Protective Role of the Immune System in Spinal Cord Injury: Immunomodulation with Altered Peptide Ligands
Spinal cord injury (SCI) is a phenomenon characterized by damage to the spinal cord and nerve roots, resulting in loss of physiological activity below the lesion. Injury to the spinal cord activates a cascade of cellular and molecular reactions in which the immune system plays an essential role, as there is an uncontrolled immune response that endows further damage to neural tissue. However, the activity of immune system at the site of injury can be modified in order to obtain a neuroprotective environment and promote SCI recovery. This strategy has been designed under the light of the innovative concept “protective autoimmunity” (PA) and can be stimulated with the use of altered peptide ligands (APL). Adequate immunomodulation with APL can be obtained with the peptide A91, which is a safe synthetic peptide derived from the myelin basic protein (MBP) that has proven to be effective in preclinical research. Immunization with A91 is carried out with the objective of preventing further damage and promoting neuroprotection. This peptide has direct influence over SCI secondary mechanisms such as inflammation, lipid peroxidation, and apoptosis. Preclinical results suggest that immunization with A91 could be an effective treatment in the clinical field, providing a better quality of life to SCI patients.
Part of the book: Recovery of Motor Function Following Spinal Cord Injury
Immune System Involvement in the Degeneration, Neuroprotection, and Restoration after Stroke
Cerebrovascular diseases are currently among the three primary causes of death worldwide and are the first cause of disability in adults. Nevertheless, there are no neuroprotective or neurorestorative therapies that have shown considerable beneficial effects, except for the FDA-approved recombinant tissue plasminogen activator (rtPA), which has been used for decades for the treatment of stroke and its effectiveness is still controversial. This is why it is very important to develop effective therapeutic options. In order to achieve this objective, it is essential to recognize the secondary mechanisms involved in the pathological development. The immunological system is one of these mechanisms that participate during the acute and chronic phases of disease, both in deleterious and beneficial manners. It is known that the immune system’s duality contributes to the ischemic injury through proinflammatory cytokine (tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6)), and oxygen reactive species production, etc. Nevertheless, it also provides protection and even restoration through anti-inflammatory cytokine (interleukin-4 (IL-4), interleukin-10 (IL-10), transforming growth factor-β (TGF-β)), and growth factor (brain-derived neurotrophic factor (BDNF), insulin-like growth factor-1 (IGF-1), neurotrophin-3 (NT-3), neurotrophin-4 (NT-4)) production. This states that innovative therapeutic options must be proposed with the goal of protecting and restoring the tissue after the ischemic event. Such therapies are exposed in the present chapter.
Part of the book: Ischemic Stroke
Pharmacological and Nonpharmacological Therapeutic Strategies Based on the Pathophysiology of Acute and Chronic Spinal Cord Injury
Spinal cord injury (SCI) induces a series of anatomic and physiological disorders which have severe repercussions on neural function. SCI is classified chronologically into an acute (primary and secondary phase) and a chronic phase. The primary phase results directly from the initial trauma and is comprised of disturbances in neural tissue (mainly axons), blood vessels, and spinal shock. Secondary injury results from a series of time-dependent pathophysiological changes, beginning in the first minutes after SCI and lasting days and weeks. This phase is characterized by biochemical and immunological alterations in the injury site and periphery, leading to neuronal over-excitation, apoptosis, and axonal demyelination. In chronic stages, the pathophysiology consists of disturbances in fiber organization, oligodendrocyte apoptosis, fibroglial scar formation, and cyst formation, leading to parenchymal alterations such as syringomyelia and hydromyelia hindering the possibility for functional basal axonal regeneration. This chapter will review a wide range of pharmacological and nonpharmacological therapeutic strategies in preclinical and clinical phases, each targeting different pathological mechanisms of SCI in acute and chronic stages of SCI; taking into account limitations, advances, scope, and new trends. The chapter focuses on the general aspects of SCI pathophysiology, pharmacological and nonpharmacological treatments acute and chronic stages of SCI.
Part of the book: Essentials of Spinal Cord Injury Medicine
Trends in Neuroprotective Strategies after Spinal Cord Injury: State of the Art
Spinal cord injury (SCI) is an important pathology leading to possibly fatal consequences. The most common repercussions are those affecting motor and sensitivity skills. SCI-damage occurs in its first phase—as a result of the lesion mechanism (contusion, compression, transection, and primary lesion). After this primary damage, there is a second phase with further deleterious effects on neural degeneration and tissue restoration. At the moment, several investigation groups are working on developing therapeutic strategies to induce neuroprotection. This chapter pretends to introduce the reader to a wide range of these therapies, particularly those with promising results and tested in preclinical and clinical studies. In the first section, physiopathology of SCI will be addressed. Afterwards, the chapter will review neuroprotective strategies such as cyclooxygenase, calpain, and apoptosis inhibitors. Finally, the effect of immunophilin ligands, neural-derived peptides, antioxidants, hypoglycemic agent, gonadal hormones, Na channel blockers, and transplant of cultured cells will also be reviewed.
Part of the book: Neuroprotection
Available Therapeutics after a Stroke: Current and Promising Options
Morbidity and mortality after a cerebrovascular event have increased during the past few years, even after extensive efforts have been made concerning research in prevention, acute treatment, pharmacotherapy, revascularization, and rehabilitation. The functional deficits that arise from an ischemic event are related to the increasing chronic disability that results from lower mortality rates. More people are becoming chronically disabled; currently, as much as 90% of survivors are affected and face difficulties to continue with daily life activities. In this chapter, we briefly review the pathophysiology of ischemia and immediate clinical attention to the event. We argue about the need to seek new pharmacological and non-pharmacological alternatives and discuss the most representative in the field of neuroprotection and neurorestoration. In addition, we review the most relevant dietetic strategies and physical rehabilitation therapies, all aimed at improving the survivors’ quality of life.
Part of the book: New Insight into Cerebrovascular Diseases
Neuroprotective and Neurorestorative Properties of Copolymer-1: Its Immunomodulating Effects on Ischemic StrokeView all chapters
Stroke is a pathology of great relevance worldwide as it currently occupies the second motif of death and the third reason of disability. Although exits some therapies that are used successfully in the clinic, a very high percentage of patients do not have the opportunity to benefit from them; therefore, it is imperative to propose other alternatives that may favor more patients. In this chapter, we briefly review the inflammatory response induced by stroke and also its deleterious and protective effects. We will describe the characteristics of copolymer-1 and the effects that this compound has shown in models of cerebral ischemia.
Part of the book: Neuroprotection