Hayder M. Al-kuraishy

By Hayder M. Al-kuraishy and Ali I. Al-Gareeb

Vinpocetine (VPN) is a synthetic ethyl-ester derivative of the alkaloid apovincamine from Vinca minor leaves. VPN is a selective inhibitor of phosphodiesterase type 1 (PDE1) has potential neurological effects through inhibition of voltage gated sodium channel and reduction of neuronal calcium influx. VPN have noteworthy antioxidant, anti-inflammatory and anti-apoptotic effects with inhibitory effect on glial and astrocyte cells during and following ischemic stroke (IS). VPN is effective as an adjuvant therapy in the management of epilepsy; it reduces seizure frequency by 50% in a dose of 2 mg/kg/day. VPN improves psychomotor performances through modulation of brain monoamine pathway mainly on dopamine and serotonin, which play an integral role in attenuation of depressive symptoms. VPN recover cognitive functions and spatial memory through inhibition of hippocampal and cortical PDE-1with augmentation of cAMP/cGMP ratio, enhancement of cholinergic neurotransmission and inhibition of neuronal inflammatory mediators. Therefore, VPN is an effective agent in the management of ischemic stroke and plays an integral role in the prevention and attenuation of post-stroke epilepsy, depression and cognitive deficit through direct cAMP/cGMP-dependent pathway or indirectly through anti-inflammatory and anti-oxidant effects.

Part of the book: Ischemic Stroke

By Hayder M. Alkuraishy, Ali I. Al-Gareeb and Naseer A. Al-Harchan

Orexin is a neuropeptide secreted from the lateral hypothalamus and prefrontal cortex concerned in wakefulness and excitement. This study aimed to review the possible neurobiological effect of orexin. A diversity of search strategies was adopted and assumed which included electronic database searches of Medline and PubMed using MeSH terms, keywords, and title words. Orexin plays a vital role in activation of learning, memory acquisition, and consolidation through activation of the monoaminergic system, which affects cognitive flexibility and cognitive function. Orexin stimulates adrenocorticotrophin (ACTH) and corticosteroid secretions via activation of the central corticotropin-releasing hormone (CRH). Cerebrospinal (CSF) and serum orexin serum levels are reduced in depression, schizophrenia, and narcolepsy. However, high orexin serum levels are revealed in drug addictions. Regarding neurodegenerative brain diseases, CSF and serum orexin levels are reduced in Parkinson’s disease (PD), Alzheimer’s disease (AD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and multiple sclerosis (MS). Orexin antagonist leads to significant reduction of sympathetic overactivity during withdrawal syndrome. Also, orexin antagonist improves sleep pattern. The orexinergic system is involved in different psychiatric and neurological disorders; therefore targeting of this system could be a possible novel pathway in the management of these disorders. In addition measurement of CSF and serum orexin levels might predict the relapse and withdrawal of addict patients.

Part of the book: Weight Management

By Hayder M. Al-Kuraishy, Marwa S. Al-Niemi, Nawar R. Hussain, Ali I. Al-Gareeb, Nasser A. Al-Harchan and Azhar H. Al-Kurashi

Novel coronavirus (COVID-19) led to infected pneumonia and acute respiratory distress syndrome (ARDS) and acute kidney injury (AKI). The entry-point receptor for COVID-19 is angiotensin-converting enzyme 2 (ACE2) at lung, and dipeptidyl peptidase-4 (DPP-4) is a receptor for Middle East respiratory syndrome coronavirus (MERS-CoV). There is 80% similarity between MERS-CoV and COVID-19. This study was planned to review the potential link between the incidence and severity of COVID-19 regarding the modulation of DPP-4 and ACE2 by DPP-4 and renin angiotensin system (RAS). In COVID-19, SARS-CoV2 binds ACE2 which is highly expressed by the epithelial cells of the blood vessel, intestine, and lung. However, pulmonary ACE2 seems to be a protective defense pathway during ARDS. DPP-4 is not concerned with the entry of COVID-19 but mediates the inflammatory reactions and cytokine storm that induced ARDS and AKI by COVID-19. The interaction between DPP4i and RAS inhibitors seem to augment the expression of AT2 receptor and ACE2 which are under extensive researches to find the pathophysiological pathway of COVID-19 infection. This beneficial interaction between DPP4i and RAS shed light for possible attenuation of COVID-19-induced ARDS and AKI mainly in critically ill patients with systemic hypertension.

Part of the book: Selected Chapters from the Renin-Angiotensin System