Physiopathology of ischemic stroke and its modulation using memantine: evidence from preclinical stroke

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From: Neural Regeneration Research(Vol. 16, Issue 3)
Publisher: Medknow Publications and Media Pvt. Ltd.
Document Type: Report
Length: 6,858 words
Lexile Measure: 1480L

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Byline: Hilda. Martinez-Coria, Isabel. Arrieta-Cruz, Maria-Esther. Cruz, Hector. Lopez-Valdes

Ischemic stroke is the most common type of cerebrovascular disease and is caused by an interruption of blood flow in the brain. In this disease, two different damage areas are identifying: the lesion core, in which cells quickly die; and the penumbra (surrounding the lesion core), in which cells are functionally weakened but may recover and restore their functions. The currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy, but they have a short therapeutic window (4.5 and 6 hours after stroke onset, respectively) and a low percentage of stroke patients actually receive these treatments. Memantine is an approved drug for the treatment of Alzheimer's disease. Memantine is a noncompetitive, low affinity and use-dependent antagonist of N-methyl-D-aspartate glutamate receptor. Memantine has several advantages over developing a new drug to treat focal ischemic stroke, but the most important is that it has sufficient safe probes in preclinical models and humans, and if the preclinical studies provide more evidence about pharmacological actions in tissue protection and repair, this could help to increase the number of clinical trials. The present review summarizes the physiopathology of isquemic stroke and the pharmacological actions in neuroprotection and neuroplasticity of memantine in the post stroke stage of preclinical stroke models, to illustrate their potential to improve functional recovery in human patients.

Introduction

Among cerebrovascular diseases, stroke is the most frequent. Worldwide, stroke is the second most common cause of death and the third most common cause of disability (Feigin et al., 2017). There are two main types of stroke, hemorrhagic and ischemic. The former represents about 15% while the latter accounts for the remaining 85%. Focal ischemic stroke is the most common and is caused by the occlusion of a cerebral artery and can be local or distal. Locally, the main cause is the formation of a thrombus or an atherosclerotic plaque. Distally, an embolus (clot) forms in another blood vessel and travels to the brain and occludes a cerebral artery (Brouns and De Deyn, 2009; Moskowitz et al., 2010).

Currently approved treatments for ischemic stroke are the recombinant tissue plasminogen activator and endovascular thrombectomy, which focus on saving the penumbra cells and limit the infarct core enlargement by removing the occlusion in the artery, but they are effective only if started within a few hours of the onset of the stroke. Treatment with recombinant tissue plasminogen activator, a fibrinolytic agent, is effective if applied within the first four and a half hours of stroke onset, however, there is a potential risk of hemorrhage (del Zoppo, 2013). Mechanical thrombectomy, on the other hand, shows benefits when applied within the first six hours of ischemic stroke onset, but the patients should be selected by appropriate imaging and treated by experienced operators (Asadi et al., 2015). Both treatments are effective but have a very limited therapeutic window and few patients have access to them or are suitable candidates. Moreover, in some cases, these treatments...

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Gale Document Number: GALE|A636783700