The composition of cerebrospinal fluid and comparison with serum [58, 59].
\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"Milestone",originalUrl:"/media/original/124"}},components:[{type:"htmlEditorComponent",content:'
Barely three months into the new year and we are happy to announce a monumental milestone reached - 150 million downloads.
\n\nThis achievement solidifies IntechOpen’s place as a pioneer in Open Access publishing and the home to some of the most relevant scientific research available through Open Access.
\n\nWe are so proud to have worked with so many bright minds throughout the years who have helped us spread knowledge through the power of Open Access and we look forward to continuing to support some of the greatest thinkers of our day.
\n\nThank you for making IntechOpen your place of learning, sharing, and discovery, and here’s to 150 million more!
\n\n\n\n\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"2583",leadTitle:null,fullTitle:"Sepsis - An Ongoing and Significant Challenge",title:"Sepsis",subtitle:"An Ongoing and Significant Challenge",reviewType:"peer-reviewed",abstract:"Sepsis is the major cause of death in non-cardiologic intensive care units around the world. Every year, billions of dollars are consumed in the treatment of sepsis and in research to understand its complex pathophysiology and therefore obtain future therapeutic opportunities. Despite the efforts of the scientists and medical practitioners, the mortality rates are still high and the incidence of sepsis is increasing. In this book we provide an update on several aspects of sepsis. Starting from the history of the disease and finishing with treatment of sepsis-associated organ dysfunctions, this book offers a wide scope of well-written and complete reviews concerning pathophysiological and therapeutic characteristics of sepsis. We hope that the work of the authors will provide a significant forum of discussion on the topic, and increase the awareness of the healthcare team regarding the important aspects of early recognition and treatment of this severe condition.",isbn:null,printIsbn:"978-953-51-0780-4",pdfIsbn:"978-953-51-7032-7",doi:"10.5772/2958",price:139,priceEur:155,priceUsd:179,slug:"sepsis-an-ongoing-and-significant-challenge",numberOfPages:422,isOpenForSubmission:!1,isInWos:1,isInBkci:!1,hash:"85121c8c358a97497c254ca2832be903",bookSignature:"Luciano Azevedo",publishedDate:"October 3rd 2012",coverURL:"https://cdn.intechopen.com/books/images_new/2583.jpg",numberOfDownloads:88340,numberOfWosCitations:35,numberOfCrossrefCitations:27,numberOfCrossrefCitationsByBook:2,numberOfDimensionsCitations:63,numberOfDimensionsCitationsByBook:3,hasAltmetrics:1,numberOfTotalCitations:125,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"December 7th 2011",dateEndSecondStepPublish:"January 11th 2012",dateEndThirdStepPublish:"April 16th 2012",dateEndFourthStepPublish:"July 15th 2012",dateEndFifthStepPublish:"August 14th 2012",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"72846",title:"Prof.",name:"Luciano",middleName:null,surname:"Azevedo",slug:"luciano-azevedo",fullName:"Luciano Azevedo",profilePictureURL:"https://mts.intechopen.com/storage/users/72846/images/3578_n.jpg",biography:"Dr. Luciano Azevedo obtained his medical degree from Federal University of Paraíba, Brazil, in 1996. After deciding to study critical care, he moved to São Paulo where he finished medical residencies in Internal Medicine and Critical Care Medicine at the University of São Paulo in 1998 and 1999, respectively. By this time, he was completely absorbed by the study of sepsis and this led him to complete his PhD in this area at the University of São Paulo in 2004. Nowadays, he is a professor at the Emergency Medicine Department at the University of São Paulo and the coordinator of the Intensive Care and Anesthesiology Experimental Laboratory at the Instituto Sirio-Libanes de Ensino e Pesquisa in São Paulo. 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Cerebrospinal fluid (CSF) is located in the brain ventricles, the cranial and spinal subarachnoid spaces [1, 2]. It acts as a cushion and plays a significant role in brain development, in the regulation of the interstitial fluid of the brain parenchyma and healthy neuronal functioning [1]. CSF is mainly produced from the choroid plexuses and mainly absorbed through arachnoid villi. The mean CSF volume is 150 ml, with 125 ml in subarachnoid spaces and 25 ml in the ventricles. In this chapter, historical understanding, anatomy, histology, embryology of ventricles, and physiology of CSF will be discussed.
In ancient times, ventricles were thought to be the site of emotions, mind, judgment, and memory. Hippocrates (460–375 BC), described congenital hydrocephalus as ‘water’ around the brain [3]. Most likely, Aristotle (384–322 BC) was the first one who noticed the presence of brain cavities, especially the lateral ventricles [4]. A Greek physician, Herophilos of Chalcedon (335–280 BC) was the true discoverer of the first human cadavers dissections [5]. He also described the choroid plexuses [6]. Erasistratus of Ceos (304–250 BC), a scholar of Herophilus, suggested the ventricular theory [7]. Rufus of Ephesus (110–180), master of Galen of Pergamum, elaborated the lateral, third, and fourth ventricles and the mesencephalic aqueduct [7]. Galen (130–200) also described the ventricular system detailly and mentioned pneuma, a breath that arises from the cosmos which circulates through the brain cavities, and serves as a mediator between body and soul [7, 8]. He also specified that obstruction of the ventricular system causes seizures. In Anathomia (1316), Mondino de Luzzi (1270–1326) preserved the tricameral theory for cerebral ventricles, which is mostly influenced by Galenic tradition [9]. Leonardo da Vinci (1452–1519) made the first ventriculography on the ox brain and extracted a three-dimensional template that showed the shape of the ventricular labyrinth [2, 10]. In 1859, a German anatomist and surgeon Benedict Stilling (1810–1879) describe the terminal ventricle as a cystic cavity lined by ependymal cells located in the conus medullaris for the first time [7]. Then, in 1875, Krause called it the fifth ventricle, named after him as Krause’s ventricle [7].
Cerebrospinal fluid is discovered by E. Swedenborg (1688–1772) [11]. In 1747, a Swiss physician A. von Haller (1708–1777), presented that in the brain the ‘water’ is secreted into the ventricles and absorbed in the veins. Hydrocephalus has resulted from excess secretion, which descends to the skull base and into the “spinal marrow” [12]. Domenico Felice Antonio Cotugno [13] was the one who first defined the connection between cerebral ventricles and subarachnoid space. A French physiologist, F.J. Magendie (1783–1855) also confirmed this finding [13]. An opening in the roof of the fourth ventricle, foramen Magendie, was discovered by Magendie, however, erroneously mentioned that CSF was secreted by the pia mater [14]. T. Willis (1621–1675), an English physician, described “a liquid” in the aqueduct of Sylvius that connects the ventricles, and continued that the consistency of the “liquid” is altered in “epidemic fever,” i.e., meningitis [15]. In 1891, W.E. Wynter (1860–1945) by tapping the spinal subarachnoidal space treated tuberculous meningitis [16]. H. Quincke (1842–1922), a German internist and surgeon popularized lumbar puncture and advocated its use for diagnostic and therapeutic reasons [17]. In 1912, a neurologist W. Mestrezat (1883–1928) described the chemical composition of the CSF accurately [18], and in 1914, a pioneer neurosurgeon H.W. Cushing (1869–1939), made it clear that the CSF is secreted by the choroid plexus [19].
In the brain, there are 4 ventricles: 2 lateral ventricles, the third ventricle in the diencephalon, and the fourth ventricle in the hindbrain (Figure 1) [2]. It is continuous with the central canal of the spinal cord caudally.
Illustration of ventricular system anatomy [
The lateral ventricle is a C-shaped cavity with a capacity of 7–10 ml [2]. It encompasses the thalamus and diencephalon and is divided into five segments. The lateral ventricle has body (central portion), atrium (trigone), and 3 horns (cornua); anterior (frontal), posterior (occipital), and inferior (temporal) horns [21, 22]. The corpus callosum forms the roof of the lateral ventricle, and the posterior portion of the septum pellucidum lies medially. Septum pellucidum is a thin vertical sheet of nervous tissue covered with ependyma on both sides of the ventricles. The caudate nucleus, the lateral dorsal surface of the thalamus, the anterior part of the body of the fornix, the choroid plexus, and stria terminalis form the floor of the lateral ventricle.
The body of the lateral ventricle lies within the parietal lobe [2]. The anterior limit is the interventricular foramen and the posterior limit is the splenium of the corpus callosum. The inferior surface of the body of the corpus callosum forms the roof. Mostly septum pellucidum forms the medial wall and in the lower part of the medial wall, there is the body of the fornix. From medial to lateral; choroid fissure, choroid plexus that invaginate into the lateral ventricle through a slit space between the fornix and upper surface of the thalamus, the lateral part of the superior surface of the thalamus, thalamostriate vein, stria terminalis, and the body of the caudate nucleus forms the concave floor.
The frontal horn is located anterior to the interventricular foramen and moves anteriorly and slightly lateral and downward to lie in the frontal lobe [2]. It has an anterior and medial wall, a roof, and a floor. The posterior surface of the genu of the corpus callosum and the rostrum forms the anterior wall. The medial wall is formed by the septum pellucidum. The roof is formed by the inferior surface or anterior part of the body of the corpus callosum. By a majority, the floor is formed by the head of the caudate nucleus, while the upper surface of the rostrum of the corpus callosum forms a small portion on the medial side.
Posterior horn turn inversely and medially to lie in the occipital lobe [2, 21, 22]. It is mostly asymmetrical. The tapetum (sheet of fibers of corpus callosum) forms the roof and lateral wall. The posteriorly sweeping optic radiation is separated with tapetum from the cavity of the posterior horn. The upper part of the medial wall is formed by the forceps major (fibers of the occipital lobe sweeping backward). The calcar avis, the lower part of the medial wall corresponds to the in-folding of the anterior part of the calcarine sulcus. There is no choroid plexus at the anterior and posterior horn.
The inferior horn is located inside of the temporal lobe, and it is the longest and largest of the 3 horns [2]. It creates a trajectory around the posterior end of the thalamus, goes posterolaterally and anteriorly into the temporal lobe. The roof is covered laterally by the inferior surface of the tapetum of the corpus callosum and medially by the tail of the caudate nucleus and stria terminalis. The floor is formed medially by collateral eminence produced by the hippocampus and laterally by a collateral sulcus. The hippocampal fibers form the alveus which covers the ventricular surface and form the fimbria converges medially. On the most medial side on the floor, the choroid plexus passes through the choroid fissure rest. The choroid plexus passes from the lateral ventricle into the inferior horn. The amygdaloid complex is situated at the anterior end of the inferior horn [21, 22]. The atrium (collateral trigone) connects the body of the lateral ventricle with the occipital and temporal horns.
Interventricular foramen of Monro is the communication between lateral and third ventricles, and it is bordered by the fornix, caudate nucleus, septum pellucidum, corpus callosum, and thalamus. The size of the ventricles determined the size and shape of the foramen. If the ventricular size is big, each foramen is rounded-shaped. As the ventricular size decreases, the foramen takes a crescent shape. The medial posterior choroidal arteries, the septal veins, and the superior choroidal vein pass through this structure [23].
The third ventricle is located in-between the 2 thalami and some portion of the hypothalamus. This narrow vertical cavity of the diencephalon communicates with the lateral ventricles in the anterosuperior aspect, while on its posteroinferior aspect through the cerebral aqueduct of Sylvius, it communicates with the fourth ventricle [2]. The third ventricular cavity is lined by ependyma and is traversed by massa intermedia (interthalamic adhesion) that connects the 2 thalami which are located posterior to the foramen of Monro. It has a roof, a floor, 2 lateral walls, anterior and posterior walls.
A sheet of ependyma forms the
From the interventricular foramen to the cerebral aqueduct, a curved hypothalamic sulcus extends and forms the
The anterior recess (vulva of the ventricle), infundibular recess, optic recess, pineal recess, and supraspinal recess are the protrusions of the third ventricle into surrounding structures [24].
The Sylvian aqueduct measures 18 mm approximately and it is the narrowest part of the brain ventricular system. From the second fetal month, the luminal size of the aqueduct reduces due to the development of neighboring neural tissue [25]. The interventricular blockade mostly occurs here.
The fourth ventricle is a wide, diamond-shaped cavity of the hindbrain [2]. It is located posterior to the pons and rostral part of the medulla, and anteroinferior to the cerebellum. On the sagittal section, it is seen as triangular, and on the horizontal section, it is seen as a rhomboidal shape. The floor of the fourth ventricle is also named the rhomboid fossa. It is continuous superiorly with the cerebral aqueduct and inferiorly with the central canal of the spinal cord. The fourth ventricle has 2
The fourth ventricle is bounded superolateral by the superior cerebellar peduncle and inferolateral by cuneate and gracile tubercles and inferior cerebellar peduncles.
Two superior cerebellar peduncles form the cephalic portion of the roof. Their medial margins overlap the ventricle on reaching the inferior colliculi. Superior medullary velum bridges the space between the superior cerebellar peduncle. Dorsally, it is covered by the lingula of the superior vermis of the cerebellum. The caudal portion of the roof is covered by the inferior medullary velum, which is formed by the tela choroidea of the fourth ventricle and the ventricular ependyma.
The lateral foramen of Luschka (located near the flocculus of the cerebellum) and the median foramen of Magendie (a large midline aperture, located in the roof of the ventricle at the lower part of inferior medullary velum) are the openings where the fourth ventricle communicates with the subarachnoid space. Mostly, the CSF passes through the medial foramen into the cerebellomedullary cistern, i.e., cisterna magna. The cerebral aqueduct does not contain choroid plexus.
Ependymocytes (ependyma), which are a special type of cells that are columnar or cuboidal epithelium derived from the neuroepithelium cover the ventricular system of the brain [2]. The choroid plexus lies just below the ependymal layer and is responsible for CSF production.
A layer of subependymal glial cells tighten with the astrocyte processes and form the blood-brain barrier. Circumventricular organs are lack this barrier and have fenestrated capillaries with increased permeability. They have secretory and sensory functions. These are the area postrema, median eminence, pineal gland, organum vasculum of lamina terminalis, neurohypophysis, subcommissural organs, and subfornical organ [26]. The ciliary movement is oriented in the anteroposterior neuroaxis which is essential for the movement of CSF.
The ventricular system of the brain develops from the cavity of the neural tube [2]. Around the fourth week of gestation the neural tube is formed. Soon after, the spinal neurocele closes, and the neural cavity is separated from the amniotic cavity.
The choroid plexuses firstly appear in the 4th ventricle on the 41st day [27]. Different embryonic tissues give rise to cerebral and spinal meninges. At the third month of intrauterine life, the three meningeal layers differentiate [1]. The choroid plexus epithelium which is derived from the neural tube is continuous with the ependyma. The leptomeningeal axis is derived from the paraxial mesoderm. From the 26th week, cerebral veins dilate in the superior sagittal sinus at their anastomosis site. In the 35th week, the arachnoid villi are formed. The arachnoid stroma lined by endothelium protrudes into the lumen of the superior sagittal sinus via a defect in the dura mater. At the 39th week, real arachnoid granulations appear [28] and continue to develop around 18 months [29].
The choroid plexus of the lateral ventricle is supplied from the anterior and posterior choroidal arteries, which are the internal carotid artery and the posterior cerebral artery branches respectively [2]. The posterior choroidal arteries supply the choroid plexus of the third ventricle. The anterior and posterior inferior cerebellar arteries supply the choroid plexus of the fourth ventricle.
Normal CSF formation rate is about 0.35 ml/min for adults, and this ranges from 400 to 600 ml per day [1, 30, 31]. CSF is renewed about four times a day. CSF production is elevated nocturnally and this may be due to cerebral metabolism alterations during sleep [32]. CSF formation also alters in disease states [33]. The choroid plexuses of the lateral ventricles and the tela choroidea of the third and fourth ventricles are responsible for most of the CSF secretion (60–70%) [1, 30]. Other sources of CSF are interstitial fluid, ependyma, and capillaries.
An asymmetrically positioned ion transporters at the blood- and CSF-facing membranes mediates fluid secretion into the ventricles. The choroid plexus epithelium is like the kidney proximal tubule, and transfer copious volumes of fluid [34]. The net transfer of sodium (Na+) and chloride (Cl−) from blood to ventricles determine CSF production [35, 36, 37]. From plasma across the basolateral membrane, Na+ entry into choroid plexus epithelium is on a downhill gradient. Potassium (K+), Cl−, and bicarbonate (HCO3−) move downhill across the apical membrane into CSF at the other side of the choroid cell. These downhill ionic movements are set up by uphill active transport through the primary Na+ pump both basolaterally and apically. This process requires chemical energy as adenosine triphosphate [ATP]. Choroid cell Na+ concentration is kept relatively low by active Na+ pumping into CSF [38] so a basolateral inward driving force for Na+ transport from plasma into the epithelium was established [39].
For fluid formation the epithelial transport polarity is essential. From blood to CSF net fluid movement is enabled by the polar distribution of certain active transporters and passive channels. Streaming of ions and water were mediated by basolateral (interstitial) and apical (CSF) transporters and channels.
The direction of fluxes in CSF formation is mostly from interstitium to parenchyma to ventricles. K+ and Cl− passive diffusion (apical efflux) were allowed by channels into nascent CSF [40]. CSF formation is mainly produced by net secretion of Na+, Cl−, and HCO3−. Other ions, i.e., K+, Mg2+, and Ca2+ also have a role. Through the apical membrane water osmotically follows ion transport.
In CSF formation, the pivotal initiating step is the primary active transport of Na+ from choroidal epithelium to ventricle [41]. Na+, K+-ATPase creates the electrochemical gradient, generates ATP, and empowers Na+ pumping [42]. While CSF is being produced, the apical Na+ efflux is balanced by permanent basolateral Na+ influx through the epithelial Na+ channel (ENaC) and Na+-inward transport coupled with HCO3−, by the Na+, HCO3− cotransporter, NBCn2/NCBE in order to equilibrate choroid pH and epithelial volume [39, 43, 44, 45].
Chloride, one of the primary anion in CSF secretion, is actively transported through the transcellular route in exchange for cellular HCO3− across the basolateral membrane [46]. Then for gathering above electrochemical equilibrium, plasma Cl− goes into the epithelium [47]. In certain circumstances, intraepithelial Cl− diffuses into CSF through the efflux arm of the Na+-K+-Cl− cotransporter [48]. The downhill diffusion of Cl− into CSF across apical Cl− channels is the main pathway by which Cl− accesses the ventricles to sustain fluid formation [40].
In the choroid plexus, HCO3− has two sources. First, in choroid plexus epithelial cells to form H+ and HCO3− ions carbonic anhydrase catalyzes the hydration of carbon dioxide (CO2) [49]. Acetazolamide inhibits CSF secretion at least 50% which indicates that carbonic anhydrase is involved in CSF secretion [50]. Additionally, via Na+-coupled HCO3− transport, HCO3− is pulled from plasma into the epithelium [43]. When the HCO3− accumulates, by two mechanisms it is ready for release through the CSF facing membrane. Firstly, in the epithelium downhill through an anion channel HCO3− diffuses into CSF [51]. Secondly, at the apical membrane HCO3− is transferred through an electrogenic Na+-coupled HCO3− cotransporter [45, 52]. CSF rich in HCO3− show increased movement of HCO3− into ventricles as CSF is produced [53].
K+ enters into the cells in two ways: from the blood by the Na+-K+-2Cl− cotransporter-1 (NKCC1) and from the interstitial fluid by the Na+-pump [54]. On both sides the influx exceeds the net flux across the cells, and thus at each membrane, there are thought to be pathways for efflux of most of the K+ that enters through K+ channels.
CSF has excretory, distributive, and buffering functions [31]. Water constitutes 99% of the CSF. After osmotically active Na+, Cl−, and HCO3− ions are transport into CSF, water follows them into the ventricles via a transcellular route by diffusing down its chemical potential gradient in the apical membrane through aquaporin 1 (AQP1) channels [55, 56]. AQP1 facilitates water transport from the interstitium to the CSF in the luminal and basolateral membrane [42]. Across the choroid plexus, transcellular water diffusion is a potential drug target to modulate CSF dynamics [55]. In regulating water molecule traffic through AQP1 channels agents structurally related to acetazolamide, furosemide, and bumetanide, and steroid hormones show promise [55, 57]. The composition of CSF and comparison with serum content were summarized in Table 1.
The choroid plexuses receive adrenergic, peptidergic, cholinergic, and serotoninergic autonomic innervation [1]. The cholinergic system increases CSF secretion while the sympathetic nervous system reduces CSF secretion. Circadian variations of CSF secretion may be regulated by the autonomic nervous system.
The targets of humoral regulation are enzymes and membrane transporters. The activity of carbonic anhydrase is regulated by the acid-base disorders, membrane carrier proteins (i.e., the NaK2Cl cotransporter), and aquaporins. Neuropeptide factors and monoamines also have a role. Atrial Natriuretic Peptide (ANP), Arginine Vasopressin (AVP) dopamine, serotonin, and melatonin receptors are present on the surface of the choroidal epithelium. ANP and AVP decrease CSF secretion [60], as ANP acts on AQP1.
Carbonic anhydrase inhibitors and loop diuretics decrease CSF secretion and turnover via enzymatic mechanisms, which could change the neuronal milieu, making prone the elderly to age-related neurodegenerative disorders.
There is a one-way rostrocaudal CSF flow in ventricular cavities and a multi-way CSF flow in subarachnoid spaces from the sites of secretion to the sites of absorption (Figure 2) [1]. CSF flow is mainly affected by the systolic pulse wave in choroidal arteries and rapid respiratory waves. In the lateral ventricles, through interventricular foramina, CSF enters the third ventricle, and through the cerebral aqueduct, it enters the fourth ventricle. Thereafter, through the foramen of Magendie CSF goes to the subarachnoid spaces. Rostrally CSF circulates to the villous sites of absorption and caudally it circulates to the spinal subarachnoid space in the cranial subarachnoid space. The spinal arachnoid villi partly absorb the CSF, and CSF circulates rostrally to the cranial subarachnoid space.
Important structures for cerebrospinal fluid circulation [
The subcommissural organ also has a role in CSF circulation. It is a differentiation of the ependyma at the rostral extremity of the cerebral aqueduct and synthesizes SCO-spondin [62]. This protein accumulates and forms Reissner fibers, which direct the CSF circulation via the cerebral aqueduct. Early during development in man, the subcommissural organ disappears. Certain forms of congenital hydrocephalus could be explained by an intrauterine abnormality of the subcommissural organ [63].
CSF circulation was determined mainly by the arterial pulse from secretion site to absorption site [1]. The main site for CSF absorption into the venous outflow system are the cranial and spinal arachnoid villi. The cribriform plate, the cranial and spinal nerve sheaths, and the adventitia of cerebral arteries may also serve as alternative pathways for CSF drainage into the lymphatic system.
Arachnoid villi or granulations are endothelium-lined finger-like protrusions of the arachnoid outer layer via the dura mater in the venous sinus lumen (Figure 3) [65]. Villous absorption of CSF both in the brain or spine is a dynamic process that adapts the filtration rate to CSF pressure. The pressure gradient among the venous sinus and subarachnoid spaces is essential to assure CSF drainage is between 3 and 5 mmHg [66]. Especially during physical exertion, spinal arachnoid villi and the epidural venous plexus offer an alternative pathway for CSF absorption.
Diagrammatic representation of a section across the top of the skull, showing the membranes of the brain, and arachnoid granulation [
The cranial and spinal nerve sheaths and ependyma can also absorb CSF with respect to pressure gradients [1]. Via Virchow-Robin perivascular spaces, absorption through the interstitial compartment happens. On meningeal sheaths, CSF absorption surfaces have also been shown, especially the meningeal recesses of cranial and spinal nerve roots (i.e., the trigeminal and cochlear nerve). In its meningeal sheath, the optic nerve exerts a long extracranial course. With constructive interference in steady-state magnetic resonance imaging, a high-intensity ring around the optic nerve was observed in hydrocephalus. This finding indicates that when needed there is also a salvage pathway for reabsorption.
When the cranial arachnoid villi capacities are exceeded, lymphatic absorption of CSF establishes an accessory pathway [1]. Particularly, this pathway is active in neonates. Arachnoid villi are completely functional after the age of 18 months. It becomes dysfunctional in the elderly due to fibrous changes of arachnoid granulations.
The cochlear aqueduct, which is located in the petrous part of the temporal bone, has a connection between the perilymphatic space of the cochlea and the subarachnoid space of the posterior cranial fossa. It is patent in 93% of cases [67]. This could clarify the effect of intracranial pressure changes on cochlear function (i.e., tinnitus after ventriculoperitoneal shunting and at high altitude).
Ventricular cavity is a dynamic pressure system. CSF pressure is defined as the intracranial pressure (ICP) in the prone position. It is the outcome of a dynamic equilibrium between CSF secretion, resistance to flow, and absorption [1]. CSF pressure can be monitored invasively with a pressure transducer placed in the brain parenchyma or via an external ventricular/lumbar drain connected to CSF spaces. On Doppler ultrasound, to evaluate CSF pressure vascular flow can be traced as a non-invasive method. CSF pressure determines ICP with physiological values. In infancy, it ranges between 3 and 4 mmHg, and in adults, it ranges between 10 and 15 mmHg. Higher values indicate intracranial hypertension. Respiratory waves, jugular venous pressure, state of arousal, abdominal pressure, the subject’s posture, and physical effort also modulate CSF flow dynamics and pressure.
The cranial content includes parenchymal, venous, and CSF compartments. CSF pressure is established by parenchymal and venous pressures. When fontanelles are open if ICP increases macrocephaly could be observed due to an increase in intracranial volume. When the fontanelles are closed, blood volume (particularly venous) reduction is seen as compensation.
Brain compliance is described as the volume needed to change ICP. It is the indication of the intracranial contents capacity to adapt to volume changes. Brain compliance is lower in men and changes with age. The volume needed to induce a 10-times increase in ICP is 8 ml in neonates, 20 ml in 2-year-old children, and 26 ml in adults. The brain volume must be considered when brain compliance is calculated (average of 335 ml in neonates and 1250 ml in young adults).
The regulation of CSF pressure occurs at the secretion, circulation, absorption phase of CSF. When intraventricular pressure is increased, the cerebral perfusion pressure (CPP) and the pressure gradient across the blood-CSF barrier decreases, and choroidal secretion is negatively affected. The concentrations of neuropeptides (ANP and AVP) in CSF and their receptor expression in the choroidal epithelium increase with CSF pressure increase and in the state of acute hydrocephalus [68, 69]. These neuropeptides cause a decreased choroidal secretion of CSF. They also induce dilatation of pial arteries to compensate for the reduction of CPP in acute hydrocephalus [70].
CSF protects the neuraxis hydromechanically. CSF plays an important role in the regulation of cerebral interstitial fluid and the neuronal environment via arranging the circulation of active molecules, electrolyte balance, and elimination of catabolites. Via CSF, the products of choroid plexus secretion are transported to their action sites. The activity of certain brain regions is modulated by impregnation by this way. However, more rapid changes of activities happen via synaptic transmission [71].
In hydrocephalus, an increased amount of fluid accumulates in the brain ventricular system [2]. Impairment in the CSF circulation at any point could lead to this disease. Mostly, abnormal enlargement of the cerebral ventricle and increased ICP are observed. The common symptoms include headache, irritability, blurred vision, vomiting, gait disturbance, and drowsiness. A rapid increase in head circumference is the main sign in infants.
Hydrocephalus can be classified as communicating or non-communicating type. Impaired absorption of CSF by the arachnoid granulations causes communicating hydrocephalus and this can be the result of any leptomeningeal processes (i.e., inflammation due to infectious or carcinomatous meningitis or hemorrhage as in acute subarachnoid hemorrhage).
Hydrocephalus can also be classified as congenital or acquired. Aqueductal stenosis is the most common cause of congenital hydrocephalus. This can be seen in the case of aqueductal atresia (genetical) or in the case of tumors of neighboring structures compressing the aqueduct or epididymitis (acquired). This results in the enlargement of both lateral and third ventricles with a normal fourth ventricle. The foramen of Magendie and Luschka could be obstructed in Chiari malformation. In this condition, the downward displacement of the cerebellum via the foramen magnum could result in internal hydrocephalus. In the case of inflammatory fibrosis of the meninges, the foramen could be obstructed and result in congenital hydrocephalus [25]. Trauma, infection, tumor, and hemorrhage could result in acquired hydrocephalus.
Here we will briefly mention the most preferred methods for hydrocephalus management.
In ventriculostomy, a hole in the ventricles is created for CSF drainage and/or ICP monitoring. External ventricular drain is placed in the ventricle. Kocher’s point is the commonest entry point on the skull which is 3–4 cm lateral to the midline and 11 cm posterior to the glabella. The frontal horn of the lateral ventricle is the target [72].
In ventricular shunting, CSF is diverted from ventricles to body compartments such as the peritoneal cavity (ventriculoperitoneal shunt), right atrium (ventriculoatrial shunt), pleural space (ventriculopleural shunt).
In order to drain the CSF directly into the basal cisterns, an incision could also be made on the floor of the third ventricle.
CSF is an essential liquid for brain homeostasis. It has a well-balanced ionic content and has a certain secretion and absorption rate. Choroid plexuses are the main secretion site, while arachnoid villi are the main absorption site. When there is disequilibrium in secretion, absorption or any obstruction in the ventricular system hydrocephalus could be seen. There are alternative treatment methods for this condition which depend on the etiology. In this chapter, we review the historical understanding of ventricular anatomy and CSF, main anatomical structures of the ventricular system, histology of embryology of the ventricular system, CSF physiology. We also briefly mentioned hydrocephalus and the main treatment alternatives.
The authors declare no conflict of interest.
atrial natriuretic peptide
aquaporin 1
arginine vasopressin
before Christ
chloride
carbondioxide
cerebral perfusion pressure
cerebrospinal fluid
epithelial Na+ channel
bicarbonate
intracranial pressure
sodium
Na-K-2Cl cotransporter-1
weight
Cerebrospinal fluid (CSF) is located in the brain ventricles, the cranial and spinal subarachnoid spaces [1, 2]. It acts as a cushion and plays a significant role in brain development, in the regulation of the interstitial fluid of the brain parenchyma and healthy neuronal functioning [1]. CSF is mainly produced from the choroid plexuses and mainly absorbed through arachnoid villi. The mean CSF volume is 150 ml, with 125 ml in subarachnoid spaces and 25 ml in the ventricles. In this chapter, historical understanding, anatomy, histology, embryology of ventricles, and physiology of CSF will be discussed.
In ancient times, ventricles were thought to be the site of emotions, mind, judgment, and memory. Hippocrates (460–375 BC), described congenital hydrocephalus as ‘water’ around the brain [3]. Most likely, Aristotle (384–322 BC) was the first one who noticed the presence of brain cavities, especially the lateral ventricles [4]. A Greek physician, Herophilos of Chalcedon (335–280 BC) was the true discoverer of the first human cadavers dissections [5]. He also described the choroid plexuses [6]. Erasistratus of Ceos (304–250 BC), a scholar of Herophilus, suggested the ventricular theory [7]. Rufus of Ephesus (110–180), master of Galen of Pergamum, elaborated the lateral, third, and fourth ventricles and the mesencephalic aqueduct [7]. Galen (130–200) also described the ventricular system detailly and mentioned pneuma, a breath that arises from the cosmos which circulates through the brain cavities, and serves as a mediator between body and soul [7, 8]. He also specified that obstruction of the ventricular system causes seizures. In Anathomia (1316), Mondino de Luzzi (1270–1326) preserved the tricameral theory for cerebral ventricles, which is mostly influenced by Galenic tradition [9]. Leonardo da Vinci (1452–1519) made the first ventriculography on the ox brain and extracted a three-dimensional template that showed the shape of the ventricular labyrinth [2, 10]. In 1859, a German anatomist and surgeon Benedict Stilling (1810–1879) describe the terminal ventricle as a cystic cavity lined by ependymal cells located in the conus medullaris for the first time [7]. Then, in 1875, Krause called it the fifth ventricle, named after him as Krause’s ventricle [7].
Cerebrospinal fluid is discovered by E. Swedenborg (1688–1772) [11]. In 1747, a Swiss physician A. von Haller (1708–1777), presented that in the brain the ‘water’ is secreted into the ventricles and absorbed in the veins. Hydrocephalus has resulted from excess secretion, which descends to the skull base and into the “spinal marrow” [12]. Domenico Felice Antonio Cotugno [13] was the one who first defined the connection between cerebral ventricles and subarachnoid space. A French physiologist, F.J. Magendie (1783–1855) also confirmed this finding [13]. An opening in the roof of the fourth ventricle, foramen Magendie, was discovered by Magendie, however, erroneously mentioned that CSF was secreted by the pia mater [14]. T. Willis (1621–1675), an English physician, described “a liquid” in the aqueduct of Sylvius that connects the ventricles, and continued that the consistency of the “liquid” is altered in “epidemic fever,” i.e., meningitis [15]. In 1891, W.E. Wynter (1860–1945) by tapping the spinal subarachnoidal space treated tuberculous meningitis [16]. H. Quincke (1842–1922), a German internist and surgeon popularized lumbar puncture and advocated its use for diagnostic and therapeutic reasons [17]. In 1912, a neurologist W. Mestrezat (1883–1928) described the chemical composition of the CSF accurately [18], and in 1914, a pioneer neurosurgeon H.W. Cushing (1869–1939), made it clear that the CSF is secreted by the choroid plexus [19].
In the brain, there are 4 ventricles: 2 lateral ventricles, the third ventricle in the diencephalon, and the fourth ventricle in the hindbrain (Figure 1) [2]. It is continuous with the central canal of the spinal cord caudally.
Illustration of ventricular system anatomy [
The lateral ventricle is a C-shaped cavity with a capacity of 7–10 ml [2]. It encompasses the thalamus and diencephalon and is divided into five segments. The lateral ventricle has body (central portion), atrium (trigone), and 3 horns (cornua); anterior (frontal), posterior (occipital), and inferior (temporal) horns [21, 22]. The corpus callosum forms the roof of the lateral ventricle, and the posterior portion of the septum pellucidum lies medially. Septum pellucidum is a thin vertical sheet of nervous tissue covered with ependyma on both sides of the ventricles. The caudate nucleus, the lateral dorsal surface of the thalamus, the anterior part of the body of the fornix, the choroid plexus, and stria terminalis form the floor of the lateral ventricle.
The body of the lateral ventricle lies within the parietal lobe [2]. The anterior limit is the interventricular foramen and the posterior limit is the splenium of the corpus callosum. The inferior surface of the body of the corpus callosum forms the roof. Mostly septum pellucidum forms the medial wall and in the lower part of the medial wall, there is the body of the fornix. From medial to lateral; choroid fissure, choroid plexus that invaginate into the lateral ventricle through a slit space between the fornix and upper surface of the thalamus, the lateral part of the superior surface of the thalamus, thalamostriate vein, stria terminalis, and the body of the caudate nucleus forms the concave floor.
The frontal horn is located anterior to the interventricular foramen and moves anteriorly and slightly lateral and downward to lie in the frontal lobe [2]. It has an anterior and medial wall, a roof, and a floor. The posterior surface of the genu of the corpus callosum and the rostrum forms the anterior wall. The medial wall is formed by the septum pellucidum. The roof is formed by the inferior surface or anterior part of the body of the corpus callosum. By a majority, the floor is formed by the head of the caudate nucleus, while the upper surface of the rostrum of the corpus callosum forms a small portion on the medial side.
Posterior horn turn inversely and medially to lie in the occipital lobe [2, 21, 22]. It is mostly asymmetrical. The tapetum (sheet of fibers of corpus callosum) forms the roof and lateral wall. The posteriorly sweeping optic radiation is separated with tapetum from the cavity of the posterior horn. The upper part of the medial wall is formed by the forceps major (fibers of the occipital lobe sweeping backward). The calcar avis, the lower part of the medial wall corresponds to the in-folding of the anterior part of the calcarine sulcus. There is no choroid plexus at the anterior and posterior horn.
The inferior horn is located inside of the temporal lobe, and it is the longest and largest of the 3 horns [2]. It creates a trajectory around the posterior end of the thalamus, goes posterolaterally and anteriorly into the temporal lobe. The roof is covered laterally by the inferior surface of the tapetum of the corpus callosum and medially by the tail of the caudate nucleus and stria terminalis. The floor is formed medially by collateral eminence produced by the hippocampus and laterally by a collateral sulcus. The hippocampal fibers form the alveus which covers the ventricular surface and form the fimbria converges medially. On the most medial side on the floor, the choroid plexus passes through the choroid fissure rest. The choroid plexus passes from the lateral ventricle into the inferior horn. The amygdaloid complex is situated at the anterior end of the inferior horn [21, 22]. The atrium (collateral trigone) connects the body of the lateral ventricle with the occipital and temporal horns.
Interventricular foramen of Monro is the communication between lateral and third ventricles, and it is bordered by the fornix, caudate nucleus, septum pellucidum, corpus callosum, and thalamus. The size of the ventricles determined the size and shape of the foramen. If the ventricular size is big, each foramen is rounded-shaped. As the ventricular size decreases, the foramen takes a crescent shape. The medial posterior choroidal arteries, the septal veins, and the superior choroidal vein pass through this structure [23].
The third ventricle is located in-between the 2 thalami and some portion of the hypothalamus. This narrow vertical cavity of the diencephalon communicates with the lateral ventricles in the anterosuperior aspect, while on its posteroinferior aspect through the cerebral aqueduct of Sylvius, it communicates with the fourth ventricle [2]. The third ventricular cavity is lined by ependyma and is traversed by massa intermedia (interthalamic adhesion) that connects the 2 thalami which are located posterior to the foramen of Monro. It has a roof, a floor, 2 lateral walls, anterior and posterior walls.
A sheet of ependyma forms the
From the interventricular foramen to the cerebral aqueduct, a curved hypothalamic sulcus extends and forms the
The anterior recess (vulva of the ventricle), infundibular recess, optic recess, pineal recess, and supraspinal recess are the protrusions of the third ventricle into surrounding structures [24].
The Sylvian aqueduct measures 18 mm approximately and it is the narrowest part of the brain ventricular system. From the second fetal month, the luminal size of the aqueduct reduces due to the development of neighboring neural tissue [25]. The interventricular blockade mostly occurs here.
The fourth ventricle is a wide, diamond-shaped cavity of the hindbrain [2]. It is located posterior to the pons and rostral part of the medulla, and anteroinferior to the cerebellum. On the sagittal section, it is seen as triangular, and on the horizontal section, it is seen as a rhomboidal shape. The floor of the fourth ventricle is also named the rhomboid fossa. It is continuous superiorly with the cerebral aqueduct and inferiorly with the central canal of the spinal cord. The fourth ventricle has 2
The fourth ventricle is bounded superolateral by the superior cerebellar peduncle and inferolateral by cuneate and gracile tubercles and inferior cerebellar peduncles.
Two superior cerebellar peduncles form the cephalic portion of the roof. Their medial margins overlap the ventricle on reaching the inferior colliculi. Superior medullary velum bridges the space between the superior cerebellar peduncle. Dorsally, it is covered by the lingula of the superior vermis of the cerebellum. The caudal portion of the roof is covered by the inferior medullary velum, which is formed by the tela choroidea of the fourth ventricle and the ventricular ependyma.
The lateral foramen of Luschka (located near the flocculus of the cerebellum) and the median foramen of Magendie (a large midline aperture, located in the roof of the ventricle at the lower part of inferior medullary velum) are the openings where the fourth ventricle communicates with the subarachnoid space. Mostly, the CSF passes through the medial foramen into the cerebellomedullary cistern, i.e., cisterna magna. The cerebral aqueduct does not contain choroid plexus.
Ependymocytes (ependyma), which are a special type of cells that are columnar or cuboidal epithelium derived from the neuroepithelium cover the ventricular system of the brain [2]. The choroid plexus lies just below the ependymal layer and is responsible for CSF production.
A layer of subependymal glial cells tighten with the astrocyte processes and form the blood-brain barrier. Circumventricular organs are lack this barrier and have fenestrated capillaries with increased permeability. They have secretory and sensory functions. These are the area postrema, median eminence, pineal gland, organum vasculum of lamina terminalis, neurohypophysis, subcommissural organs, and subfornical organ [26]. The ciliary movement is oriented in the anteroposterior neuroaxis which is essential for the movement of CSF.
The ventricular system of the brain develops from the cavity of the neural tube [2]. Around the fourth week of gestation the neural tube is formed. Soon after, the spinal neurocele closes, and the neural cavity is separated from the amniotic cavity.
The choroid plexuses firstly appear in the 4th ventricle on the 41st day [27]. Different embryonic tissues give rise to cerebral and spinal meninges. At the third month of intrauterine life, the three meningeal layers differentiate [1]. The choroid plexus epithelium which is derived from the neural tube is continuous with the ependyma. The leptomeningeal axis is derived from the paraxial mesoderm. From the 26th week, cerebral veins dilate in the superior sagittal sinus at their anastomosis site. In the 35th week, the arachnoid villi are formed. The arachnoid stroma lined by endothelium protrudes into the lumen of the superior sagittal sinus via a defect in the dura mater. At the 39th week, real arachnoid granulations appear [28] and continue to develop around 18 months [29].
The choroid plexus of the lateral ventricle is supplied from the anterior and posterior choroidal arteries, which are the internal carotid artery and the posterior cerebral artery branches respectively [2]. The posterior choroidal arteries supply the choroid plexus of the third ventricle. The anterior and posterior inferior cerebellar arteries supply the choroid plexus of the fourth ventricle.
Normal CSF formation rate is about 0.35 ml/min for adults, and this ranges from 400 to 600 ml per day [1, 30, 31]. CSF is renewed about four times a day. CSF production is elevated nocturnally and this may be due to cerebral metabolism alterations during sleep [32]. CSF formation also alters in disease states [33]. The choroid plexuses of the lateral ventricles and the tela choroidea of the third and fourth ventricles are responsible for most of the CSF secretion (60–70%) [1, 30]. Other sources of CSF are interstitial fluid, ependyma, and capillaries.
An asymmetrically positioned ion transporters at the blood- and CSF-facing membranes mediates fluid secretion into the ventricles. The choroid plexus epithelium is like the kidney proximal tubule, and transfer copious volumes of fluid [34]. The net transfer of sodium (Na+) and chloride (Cl−) from blood to ventricles determine CSF production [35, 36, 37]. From plasma across the basolateral membrane, Na+ entry into choroid plexus epithelium is on a downhill gradient. Potassium (K+), Cl−, and bicarbonate (HCO3−) move downhill across the apical membrane into CSF at the other side of the choroid cell. These downhill ionic movements are set up by uphill active transport through the primary Na+ pump both basolaterally and apically. This process requires chemical energy as adenosine triphosphate [ATP]. Choroid cell Na+ concentration is kept relatively low by active Na+ pumping into CSF [38] so a basolateral inward driving force for Na+ transport from plasma into the epithelium was established [39].
For fluid formation the epithelial transport polarity is essential. From blood to CSF net fluid movement is enabled by the polar distribution of certain active transporters and passive channels. Streaming of ions and water were mediated by basolateral (interstitial) and apical (CSF) transporters and channels.
The direction of fluxes in CSF formation is mostly from interstitium to parenchyma to ventricles. K+ and Cl− passive diffusion (apical efflux) were allowed by channels into nascent CSF [40]. CSF formation is mainly produced by net secretion of Na+, Cl−, and HCO3−. Other ions, i.e., K+, Mg2+, and Ca2+ also have a role. Through the apical membrane water osmotically follows ion transport.
In CSF formation, the pivotal initiating step is the primary active transport of Na+ from choroidal epithelium to ventricle [41]. Na+, K+-ATPase creates the electrochemical gradient, generates ATP, and empowers Na+ pumping [42]. While CSF is being produced, the apical Na+ efflux is balanced by permanent basolateral Na+ influx through the epithelial Na+ channel (ENaC) and Na+-inward transport coupled with HCO3−, by the Na+, HCO3− cotransporter, NBCn2/NCBE in order to equilibrate choroid pH and epithelial volume [39, 43, 44, 45].
Chloride, one of the primary anion in CSF secretion, is actively transported through the transcellular route in exchange for cellular HCO3− across the basolateral membrane [46]. Then for gathering above electrochemical equilibrium, plasma Cl− goes into the epithelium [47]. In certain circumstances, intraepithelial Cl− diffuses into CSF through the efflux arm of the Na+-K+-Cl− cotransporter [48]. The downhill diffusion of Cl− into CSF across apical Cl− channels is the main pathway by which Cl− accesses the ventricles to sustain fluid formation [40].
In the choroid plexus, HCO3− has two sources. First, in choroid plexus epithelial cells to form H+ and HCO3− ions carbonic anhydrase catalyzes the hydration of carbon dioxide (CO2) [49]. Acetazolamide inhibits CSF secretion at least 50% which indicates that carbonic anhydrase is involved in CSF secretion [50]. Additionally, via Na+-coupled HCO3− transport, HCO3− is pulled from plasma into the epithelium [43]. When the HCO3− accumulates, by two mechanisms it is ready for release through the CSF facing membrane. Firstly, in the epithelium downhill through an anion channel HCO3− diffuses into CSF [51]. Secondly, at the apical membrane HCO3− is transferred through an electrogenic Na+-coupled HCO3− cotransporter [45, 52]. CSF rich in HCO3− show increased movement of HCO3− into ventricles as CSF is produced [53].
K+ enters into the cells in two ways: from the blood by the Na+-K+-2Cl− cotransporter-1 (NKCC1) and from the interstitial fluid by the Na+-pump [54]. On both sides the influx exceeds the net flux across the cells, and thus at each membrane, there are thought to be pathways for efflux of most of the K+ that enters through K+ channels.
CSF has excretory, distributive, and buffering functions [31]. Water constitutes 99% of the CSF. After osmotically active Na+, Cl−, and HCO3− ions are transport into CSF, water follows them into the ventricles via a transcellular route by diffusing down its chemical potential gradient in the apical membrane through aquaporin 1 (AQP1) channels [55, 56]. AQP1 facilitates water transport from the interstitium to the CSF in the luminal and basolateral membrane [42]. Across the choroid plexus, transcellular water diffusion is a potential drug target to modulate CSF dynamics [55]. In regulating water molecule traffic through AQP1 channels agents structurally related to acetazolamide, furosemide, and bumetanide, and steroid hormones show promise [55, 57]. The composition of CSF and comparison with serum content were summarized in Table 1.
The choroid plexuses receive adrenergic, peptidergic, cholinergic, and serotoninergic autonomic innervation [1]. The cholinergic system increases CSF secretion while the sympathetic nervous system reduces CSF secretion. Circadian variations of CSF secretion may be regulated by the autonomic nervous system.
The targets of humoral regulation are enzymes and membrane transporters. The activity of carbonic anhydrase is regulated by the acid-base disorders, membrane carrier proteins (i.e., the NaK2Cl cotransporter), and aquaporins. Neuropeptide factors and monoamines also have a role. Atrial Natriuretic Peptide (ANP), Arginine Vasopressin (AVP) dopamine, serotonin, and melatonin receptors are present on the surface of the choroidal epithelium. ANP and AVP decrease CSF secretion [60], as ANP acts on AQP1.
Carbonic anhydrase inhibitors and loop diuretics decrease CSF secretion and turnover via enzymatic mechanisms, which could change the neuronal milieu, making prone the elderly to age-related neurodegenerative disorders.
There is a one-way rostrocaudal CSF flow in ventricular cavities and a multi-way CSF flow in subarachnoid spaces from the sites of secretion to the sites of absorption (Figure 2) [1]. CSF flow is mainly affected by the systolic pulse wave in choroidal arteries and rapid respiratory waves. In the lateral ventricles, through interventricular foramina, CSF enters the third ventricle, and through the cerebral aqueduct, it enters the fourth ventricle. Thereafter, through the foramen of Magendie CSF goes to the subarachnoid spaces. Rostrally CSF circulates to the villous sites of absorption and caudally it circulates to the spinal subarachnoid space in the cranial subarachnoid space. The spinal arachnoid villi partly absorb the CSF, and CSF circulates rostrally to the cranial subarachnoid space.
Important structures for cerebrospinal fluid circulation [
The subcommissural organ also has a role in CSF circulation. It is a differentiation of the ependyma at the rostral extremity of the cerebral aqueduct and synthesizes SCO-spondin [62]. This protein accumulates and forms Reissner fibers, which direct the CSF circulation via the cerebral aqueduct. Early during development in man, the subcommissural organ disappears. Certain forms of congenital hydrocephalus could be explained by an intrauterine abnormality of the subcommissural organ [63].
CSF circulation was determined mainly by the arterial pulse from secretion site to absorption site [1]. The main site for CSF absorption into the venous outflow system are the cranial and spinal arachnoid villi. The cribriform plate, the cranial and spinal nerve sheaths, and the adventitia of cerebral arteries may also serve as alternative pathways for CSF drainage into the lymphatic system.
Arachnoid villi or granulations are endothelium-lined finger-like protrusions of the arachnoid outer layer via the dura mater in the venous sinus lumen (Figure 3) [65]. Villous absorption of CSF both in the brain or spine is a dynamic process that adapts the filtration rate to CSF pressure. The pressure gradient among the venous sinus and subarachnoid spaces is essential to assure CSF drainage is between 3 and 5 mmHg [66]. Especially during physical exertion, spinal arachnoid villi and the epidural venous plexus offer an alternative pathway for CSF absorption.
Diagrammatic representation of a section across the top of the skull, showing the membranes of the brain, and arachnoid granulation [
The cranial and spinal nerve sheaths and ependyma can also absorb CSF with respect to pressure gradients [1]. Via Virchow-Robin perivascular spaces, absorption through the interstitial compartment happens. On meningeal sheaths, CSF absorption surfaces have also been shown, especially the meningeal recesses of cranial and spinal nerve roots (i.e., the trigeminal and cochlear nerve). In its meningeal sheath, the optic nerve exerts a long extracranial course. With constructive interference in steady-state magnetic resonance imaging, a high-intensity ring around the optic nerve was observed in hydrocephalus. This finding indicates that when needed there is also a salvage pathway for reabsorption.
When the cranial arachnoid villi capacities are exceeded, lymphatic absorption of CSF establishes an accessory pathway [1]. Particularly, this pathway is active in neonates. Arachnoid villi are completely functional after the age of 18 months. It becomes dysfunctional in the elderly due to fibrous changes of arachnoid granulations.
The cochlear aqueduct, which is located in the petrous part of the temporal bone, has a connection between the perilymphatic space of the cochlea and the subarachnoid space of the posterior cranial fossa. It is patent in 93% of cases [67]. This could clarify the effect of intracranial pressure changes on cochlear function (i.e., tinnitus after ventriculoperitoneal shunting and at high altitude).
Ventricular cavity is a dynamic pressure system. CSF pressure is defined as the intracranial pressure (ICP) in the prone position. It is the outcome of a dynamic equilibrium between CSF secretion, resistance to flow, and absorption [1]. CSF pressure can be monitored invasively with a pressure transducer placed in the brain parenchyma or via an external ventricular/lumbar drain connected to CSF spaces. On Doppler ultrasound, to evaluate CSF pressure vascular flow can be traced as a non-invasive method. CSF pressure determines ICP with physiological values. In infancy, it ranges between 3 and 4 mmHg, and in adults, it ranges between 10 and 15 mmHg. Higher values indicate intracranial hypertension. Respiratory waves, jugular venous pressure, state of arousal, abdominal pressure, the subject’s posture, and physical effort also modulate CSF flow dynamics and pressure.
The cranial content includes parenchymal, venous, and CSF compartments. CSF pressure is established by parenchymal and venous pressures. When fontanelles are open if ICP increases macrocephaly could be observed due to an increase in intracranial volume. When the fontanelles are closed, blood volume (particularly venous) reduction is seen as compensation.
Brain compliance is described as the volume needed to change ICP. It is the indication of the intracranial contents capacity to adapt to volume changes. Brain compliance is lower in men and changes with age. The volume needed to induce a 10-times increase in ICP is 8 ml in neonates, 20 ml in 2-year-old children, and 26 ml in adults. The brain volume must be considered when brain compliance is calculated (average of 335 ml in neonates and 1250 ml in young adults).
The regulation of CSF pressure occurs at the secretion, circulation, absorption phase of CSF. When intraventricular pressure is increased, the cerebral perfusion pressure (CPP) and the pressure gradient across the blood-CSF barrier decreases, and choroidal secretion is negatively affected. The concentrations of neuropeptides (ANP and AVP) in CSF and their receptor expression in the choroidal epithelium increase with CSF pressure increase and in the state of acute hydrocephalus [68, 69]. These neuropeptides cause a decreased choroidal secretion of CSF. They also induce dilatation of pial arteries to compensate for the reduction of CPP in acute hydrocephalus [70].
CSF protects the neuraxis hydromechanically. CSF plays an important role in the regulation of cerebral interstitial fluid and the neuronal environment via arranging the circulation of active molecules, electrolyte balance, and elimination of catabolites. Via CSF, the products of choroid plexus secretion are transported to their action sites. The activity of certain brain regions is modulated by impregnation by this way. However, more rapid changes of activities happen via synaptic transmission [71].
In hydrocephalus, an increased amount of fluid accumulates in the brain ventricular system [2]. Impairment in the CSF circulation at any point could lead to this disease. Mostly, abnormal enlargement of the cerebral ventricle and increased ICP are observed. The common symptoms include headache, irritability, blurred vision, vomiting, gait disturbance, and drowsiness. A rapid increase in head circumference is the main sign in infants.
Hydrocephalus can be classified as communicating or non-communicating type. Impaired absorption of CSF by the arachnoid granulations causes communicating hydrocephalus and this can be the result of any leptomeningeal processes (i.e., inflammation due to infectious or carcinomatous meningitis or hemorrhage as in acute subarachnoid hemorrhage).
Hydrocephalus can also be classified as congenital or acquired. Aqueductal stenosis is the most common cause of congenital hydrocephalus. This can be seen in the case of aqueductal atresia (genetical) or in the case of tumors of neighboring structures compressing the aqueduct or epididymitis (acquired). This results in the enlargement of both lateral and third ventricles with a normal fourth ventricle. The foramen of Magendie and Luschka could be obstructed in Chiari malformation. In this condition, the downward displacement of the cerebellum via the foramen magnum could result in internal hydrocephalus. In the case of inflammatory fibrosis of the meninges, the foramen could be obstructed and result in congenital hydrocephalus [25]. Trauma, infection, tumor, and hemorrhage could result in acquired hydrocephalus.
Here we will briefly mention the most preferred methods for hydrocephalus management.
In ventriculostomy, a hole in the ventricles is created for CSF drainage and/or ICP monitoring. External ventricular drain is placed in the ventricle. Kocher’s point is the commonest entry point on the skull which is 3–4 cm lateral to the midline and 11 cm posterior to the glabella. The frontal horn of the lateral ventricle is the target [72].
In ventricular shunting, CSF is diverted from ventricles to body compartments such as the peritoneal cavity (ventriculoperitoneal shunt), right atrium (ventriculoatrial shunt), pleural space (ventriculopleural shunt).
In order to drain the CSF directly into the basal cisterns, an incision could also be made on the floor of the third ventricle.
CSF is an essential liquid for brain homeostasis. It has a well-balanced ionic content and has a certain secretion and absorption rate. Choroid plexuses are the main secretion site, while arachnoid villi are the main absorption site. When there is disequilibrium in secretion, absorption or any obstruction in the ventricular system hydrocephalus could be seen. There are alternative treatment methods for this condition which depend on the etiology. In this chapter, we review the historical understanding of ventricular anatomy and CSF, main anatomical structures of the ventricular system, histology of embryology of the ventricular system, CSF physiology. We also briefly mentioned hydrocephalus and the main treatment alternatives.
The authors declare no conflict of interest.
atrial natriuretic peptide
aquaporin 1
arginine vasopressin
before Christ
chloride
carbondioxide
cerebral perfusion pressure
cerebrospinal fluid
epithelial Na+ channel
bicarbonate
intracranial pressure
sodium
Na-K-2Cl cotransporter-1
weight
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Two hundred years ago, industrial revolution in the west has transformed or evolved from mechanical production driven or powered by water, and to date, we are in an era characterised by cyber physical systems. This transformation or industrial revolution has been driven by humans using creative minds to solve problems that were confronted. The Industrial 1.0 Revolution around 1700 AD, mass production was carried out by mechanical production powered by water (steam engines), which was labour intensive. The more manpower an industrial organisation has, the more goods and services would be produced, though this could take long to reach the market but that was the industrial system at that time. From mechanical production powered by steam engines between 1700s and 1800s to the second Industrial Revolution mass production powered by electricity between 1800s and 1900s to the third Industrial Revolution powered by electronic and IT automation and finally to Industry 4.0 Revolution cyber systems in 2000 and beyond, human capital has generated innovative solutions to human problems more than ever before. 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Therefore, problems and their solutions also change. The industrial revolution which realized in the eighteenth century had some important impacts not only on the economic life but also on social structure. It was aimed to solve social problems and ensure prosperity through social policies, which is a multidisciplinary field, and consequently, the concept of welfare state emerged. The states, which had liberal concerns and traditional protection functions and reached a powerful position with their internationalist approaches, underwent a transformation period because of the economic and social developments which took place in the last quarter of the twentieth century. It has been subject of criticism that states increased the social expenses to satisfy the social needs and therefore caused an economic crisis in this period when the effects of globalization were discussed. In this study, the change and transformation process in the welfare states and their social policies at the global scale will be handled conceptually and from the historical development perspective. Making determinations about the past and present, as well as having assumptions for future, this study aims to contribute to literature.",book:{id:"7598",slug:"public-economics-and-finance",title:"Public Economics and Finance",fullTitle:"Public Economics and Finance"},signatures:"Esra Dundar Aravacik",authors:[{id:"282700",title:"Dr.",name:"Esra",middleName:null,surname:"Dündar Aravacık",slug:"esra-dundar-aravacik",fullName:"Esra Dündar Aravacık"}]},{id:"65684",title:"Theory of Public Debt and Current Reflections",slug:"theory-of-public-debt-and-current-reflections",totalDownloads:2938,totalCrossrefCites:6,totalDimensionsCites:7,abstract:"From the ancient ages to today, administrations needed continuous financing and met this financing with various sources. The process of social development necessitated public borrowing for different purposes ranging from creation of a consumer society to sell the surplus of developed countries to postwar human relations and from the development financing of developing countries to the payment of debt by debt. Particularly after World War II (1941–1945), the developed countries provided the external resources to developing countries for development financing. As a result of the increase in the mobility of capital in the process of globalization (especially short-term speculative capital investments), developing countries were dragged to the debt-interest helix problem and the external debt crises. The stabilization programs proposed by the IMF led to government guarantee of private sector external debts in the developing countries and led to a rapid increase in the public debt stock.",book:{id:"7598",slug:"public-economics-and-finance",title:"Public Economics and Finance",fullTitle:"Public Economics and Finance"},signatures:"Sibel Aybarç",authors:[{id:"286689",title:"Dr.",name:"Sibel",middleName:null,surname:"Aybarç",slug:"sibel-aybarc",fullName:"Sibel Aybarç"}]},{id:"58010",title:"Fourth Industrial Revolution: Current Practices, Challenges, and Opportunities",slug:"fourth-industrial-revolution-current-practices-challenges-and-opportunities",totalDownloads:6296,totalCrossrefCites:41,totalDimensionsCites:66,abstract:"The globalization and the competitiveness are forcing companies to rethink and to innovate their production processes following the so-called Industry 4.0 paradigm. 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This chapter aims to present the main good practices, challenges, and opportunities related to Industry 4.0 paradigm.",book:{id:"6291",slug:"digital-transformation-in-smart-manufacturing",title:"Digital Transformation in Smart Manufacturing",fullTitle:"Digital Transformation in Smart Manufacturing"},signatures:"Antonella Petrillo, Fabio De Felice, Raffaele Cioffi and Federico\nZomparelli",authors:[{id:"161682",title:"Prof.",name:"Fabio",middleName:null,surname:"De Felice",slug:"fabio-de-felice",fullName:"Fabio De Felice"},{id:"181603",title:"Dr.",name:"Antonella",middleName:null,surname:"Petrillo",slug:"antonella-petrillo",fullName:"Antonella Petrillo"},{id:"205141",title:"Dr.",name:"Federico",middleName:null,surname:"Zomparelli",slug:"federico-zomparelli",fullName:"Federico Zomparelli"},{id:"208748",title:"Dr.",name:"Raffaele",middleName:null,surname:"Cioffi",slug:"raffaele-cioffi",fullName:"Raffaele Cioffi"}]},{id:"63402",title:"Decentralized Territorial Communities and Implementation of Public Policies: The Case of Cameroon",slug:"decentralized-territorial-communities-and-implementation-of-public-policies-the-case-of-cameroon",totalDownloads:1281,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Cameroon’s Constitutional Law of 18 January 1996 enshrined decentralization as a fundamental principle of the organization of state governance, and subsequent implementing legislation affirms the central government’s commitment to transferring a number of powers to local authorities with a view to local management. Local and regional authorities then appear as an essential link in the implementation of public policies at the local level. Their genuine autonomy in financial and administrative matters is a necessary condition for achieving local development objectives. However, a review of the existing literature reveals that these communities do not have real autonomy in public policy decision-making, which is illustrated by mixed development at the local level.",book:{id:"7598",slug:"public-economics-and-finance",title:"Public Economics and Finance",fullTitle:"Public Economics and Finance"},signatures:"Guy Yakana Yombi, Mounton Chouaïbou and Lucie Yakana Agoume",authors:[{id:"257106",title:"Mr.",name:"Guy",middleName:null,surname:"Yakana Yombi",slug:"guy-yakana-yombi",fullName:"Guy Yakana Yombi"},{id:"267660",title:"MSc.",name:"Mounton",middleName:null,surname:"Chouaïbou",slug:"mounton-chouaibou",fullName:"Mounton Chouaïbou"},{id:"267661",title:"MSc.",name:"Yakana Agoume",middleName:null,surname:"Lucie",slug:"yakana-agoume-lucie",fullName:"Yakana Agoume Lucie"}]},{id:"58030",title:"Manufacturing Transformation toward Mass Customization and Personalization in the Traditional Food Industry",slug:"manufacturing-transformation-toward-mass-customization-and-personalization-in-the-traditional-food-i",totalDownloads:1576,totalCrossrefCites:2,totalDimensionsCites:2,abstract:"Digital transformation of the manufacturing process in high-tech has been underway for a long time. On the other hand, the transformation in low-tech and traditional industries progresses more slowly. Especially, the human factor is greater in the food manufacturing industry, which retains many more labor-intensive elements. This is because the development of foods was traditionally customized to the cultures of particular regions, so many foods were not suitable for mass production, which has led to the high level of personal skills. However, new trends have been shown recently in the sake manufacturing industry. Head craftsmen at a sake brewery, known as Toji, have managed the entirety of the manufacturing process and determined the length and timing of each process for hundreds of years. In these circumstances, some sake breweries have started to make sake in a new way that breaks with tradition. They implement smart manufacturing and customization to respond to diversified customer needs without altering the product price through the digitization of the manufacturing process and the formalization of personal skills. This chapter also discusses the prospects of this transition and considers its effects on the industry with theoretical framework and social background of manufacturing transformation.",book:{id:"6291",slug:"digital-transformation-in-smart-manufacturing",title:"Digital Transformation in Smart Manufacturing",fullTitle:"Digital Transformation in Smart Manufacturing"},signatures:"Daisuke Kanama",authors:[{id:"210580",title:"Associate Prof.",name:"Daisuke",middleName:null,surname:"Kanama",slug:"daisuke-kanama",fullName:"Daisuke Kanama"}]}],onlineFirstChaptersFilter:{topicId:"65",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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From\r\n1964 to 1974, he worked as Assistant in Biochemistry at the School of MedicineUniversidad Nacional de La Plata, Argentina. From 1974 to 1976, he was a Fellowof the National Institutes of Health (NIH) at the University of Connecticut, Health Center, USA. From 1985 to 2004, he served as a Full Professor oBiochemistry at the Universidad Nacional de La Plata, Argentina. He is Member ofthe National Research Council (CONICET), Argentina, and Argentine Society foBiochemistry and Molecular Biology (SAIB). His laboratory has been interested for manyears in the lipid peroxidation of biological membranes from various tissues and different species. Professor Catalá has directed twelve doctoral theses, publishedover 100 papers in peer reviewed journals, several chapters in books andtwelve edited books. Angel Catalá received awards at the 40th InternationaConference Biochemistry of Lipids 1999: Dijon (France). 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Angel Catalá belongto the Editorial Board of Journal of lipids, International Review of Biophysical ChemistryFrontiers in Membrane Physiology and Biophysics, World Journal oExperimental Medicine and Biochemistry Research International, W orld Journal oBiological Chemistry, Oxidative Medicine and Cellular Longevity, Diabetes and thePancreas, International Journal of Chronic Diseases & Therapy, International Journal oNutrition, Co-Editor of The Open Biology Journal.",institutionString:null,institution:{name:"National University of La Plata",institutionURL:null,country:{name:"Argentina"}}},editorTwo:null,editorThree:null},{id:"12",title:"Human Physiology",coverUrl:"https://cdn.intechopen.com/series_topics/covers/12.jpg",isOpenForSubmission:!0,editor:{id:"195829",title:"Prof.",name:"Kunihiro",middleName:null,surname:"Sakuma",slug:"kunihiro-sakuma",fullName:"Kunihiro Sakuma",profilePictureURL:"https://mts.intechopen.com/storage/users/195829/images/system/195829.jpg",biography:"Professor Kunihiro Sakuma, Ph.D., currently works in the Institute for Liberal Arts at the Tokyo Institute of Technology. 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University, Kuwait. His research interests include optimization, computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, and intelligent systems. Prof. Sarfraz has been a keynote/invited speaker at various platforms around the globe. He has advised/supervised more than 110 students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He has authored and/or edited around seventy books. Prof. Sarfraz is a member of various professional societies. He is a chair and member of international advisory committees and organizing committees of numerous international conferences. He is also an editor and editor in chief for various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:null},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:"Beijing University of Technology",institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Lakhno Igor Victorovich was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPhD – 1999, Kharkiv National Medical Univesity.\nDSc – 2019, PL Shupik National Academy of Postgraduate Education \nLakhno Igor has been graduated from an international training courses on reproductive medicine and family planning held in Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor of the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s a professor of the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics and gynecology department of Kharkiv Medical Academy of Postgraduate Education . He’s an author of about 200 printed works and there are 17 of them in Scopus or Web of Science databases. Lakhno Igor is a rewiever of Journal of Obstetrics and Gynaecology (Taylor and Francis), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for DSc degree \\'Pre-eclampsia: prediction, prevention and treatment”. Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: obstetrics, women’s health, fetal medicine, cardiovascular medicine.",institutionString:"V.N. Karazin Kharkiv National University",institution:{name:"Kharkiv Medical Academy of Postgraduate Education",country:{name:"Ukraine"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"243698",title:"M.D.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:"Shanxi Eye Hospital",institution:{name:"Shanxi Eye Hospital",country:{name:"China"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRZkkQAG/Profile_Picture_2022-05-09T12:55:18.jpg",biography:null,institutionString:null,institution:null},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:null},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"338222",title:"Mrs.",name:"María José",middleName:null,surname:"Lucía Mudas",slug:"maria-jose-lucia-mudas",fullName:"María José Lucía Mudas",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}},{id:"147824",title:"Mr.",name:"Pablo",middleName:null,surname:"Revuelta Sanz",slug:"pablo-revuelta-sanz",fullName:"Pablo Revuelta Sanz",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Carlos III University of Madrid",country:{name:"Spain"}}}]}},subseries:{item:{id:"15",type:"subseries",title:"Chemical Biology",keywords:"Phenolic Compounds, Essential Oils, Modification of Biomolecules, Glycobiology, Combinatorial Chemistry, Therapeutic peptides, Enzyme Inhibitors",scope:"Chemical biology spans the fields of chemistry and biology involving the application of biological and chemical molecules and techniques. In recent years, the application of chemistry to biological molecules has gained significant interest in medicinal and pharmacological studies. This topic will be devoted to understanding the interplay between biomolecules and chemical compounds, their structure and function, and their potential applications in related fields. Being a part of the biochemistry discipline, the ideas and concepts that have emerged from Chemical Biology have affected other related areas. This topic will closely deal with all emerging trends in this discipline.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/15.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11411,editor:{id:"441442",title:"Dr.",name:"Şükrü",middleName:null,surname:"Beydemir",slug:"sukru-beydemir",fullName:"Şükrü Beydemir",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003GsUoIQAV/Profile_Picture_1634557147521",biography:"Dr. Şükrü Beydemir obtained a BSc in Chemistry in 1995 from Yüzüncü Yıl University, MSc in Biochemistry in 1998, and PhD in Biochemistry in 2002 from Atatürk University, Turkey. He performed post-doctoral studies at Max-Planck Institute, Germany, and University of Florence, Italy in addition to making several scientific visits abroad. He currently works as a Full Professor of Biochemistry in the Faculty of Pharmacy, Anadolu University, Turkey. Dr. Beydemir has published over a hundred scientific papers spanning protein biochemistry, enzymology and medicinal chemistry, reviews, book chapters and presented several conferences to scientists worldwide. He has received numerous publication awards from various international scientific councils. He serves in the Editorial Board of several international journals. Dr. Beydemir is also Rector of Bilecik Şeyh Edebali University, Turkey.",institutionString:null,institution:{name:"Anadolu University",institutionURL:null,country:{name:"Turkey"}}},editorTwo:{id:"13652",title:"Prof.",name:"Deniz",middleName:null,surname:"Ekinci",slug:"deniz-ekinci",fullName:"Deniz Ekinci",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002aYLT1QAO/Profile_Picture_1634557223079",biography:"Dr. Deniz Ekinci obtained a BSc in Chemistry in 2004, MSc in Biochemistry in 2006, and PhD in Biochemistry in 2009 from Atatürk University, Turkey. 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