Neurogenesis and Inflammation after Ischemic Stroke: What is Known and Where We Go from Here

Abstract

This review covers the pathogenesis of ischemic stroke and future directions regarding therapeutic options after injury. Ischemic stroke is a devastating disease process affecting millions of people worldwide every year. The mechanisms underlying the pathophysiology of stroke are not fully understood but there is increasing evidence demonstrating the contribution of inflammation to the drastic changes after cerebral ischemia. This inflammation not only immediately affects the infarcted tissue but also causes long-term damage in the ischemic penumbra. Furthermore, the interaction between inflammation and subsequent neurogenesis is not well understood but the close relationship between these two processes has garnered significant interest in the last decade or so. Current approved therapy for stroke involving pharmacological thrombolysis is limited in its efficacy and new treatment strategies need to be investigated. Research aimed at new therapies is largely about transplantation of neural stem cells and using endogenous progenitor cells to promote brain repair. By understanding the interaction between inflammation and neurogenesis, new potential therapies could be developed to further establish brain repair mechanisms.

Myeloperoxidase Inhibition Increases Neurogenesis after Ischemic Stroke

“…Thus, similar to our previous findings (Forghani et al, 2015), MPO inhibition improved functional outcome on our battery of behavioral tests covering motor, sensory, and reflex functions. While the dominant mechanism for the improvement is from direct inhibition of MPO activity, we wondered whether neurogenesis increased the given emerging associations between neuroinflammation and neurogenesis (Tobin et al, 2014).…”

“…On the other hand, MPO deficiency has not been found to significantly impact mortality (Kutter, 1998;Lanza, 1998;Kutter et al, 2000), making MPO a potential target for human translation. NSCs and neural precursor cells can undergo asymmetric cell division and maintain NSC pools, allowing for damaged brain repair (Tobin et al, 2014). Thus, part of the beneficial effects of MPO inhibition may be from increased neurogenesis.…”

“…While most of the NSCs die shortly after proliferation, in human stroke patients, surviving NSCs in the SVZ can differentiate into neuroblasts and migrate into the olfactory bulb (Curtis et al, 2007). The neuroblasts can further migrate to ischemic striatum and cortex, and mature into functional neurons (Jin et al, 2003;Zhang et al, 2004;Kim et al, 2009;Tobin et al, 2014). Ischemic brain injury also results in a rapid increase of inflammatory cells, such as neutrophils, monocytes, and activated microglia, in the damaged brain.…”

“…While neurogenesis is increased after stroke, the relationship between inflammation and neurogenesis in stroke is currently not well understood (Tobin et al, 2014). However, it is known that the inflammatory endotoxin lipopolysaccharide can increase microglial activation (Monje et al, 2003) and inhibit neurogenesis (Ekdahl et al, 2003;Cacci et al, 2008).…”

Современные Возможности Идентификации Новых Молекул-Мишеней Для Фармакологической Коррекции Проницаемости Гематоэнцефалического Барьера

“…Èìåííî âîñïàëåíèå ÿâëÿåòñÿ òèïè÷íîé ðåàêöèåé íà äåéñòâèå èíôåêöèîííûõ àãåíòîâ, à òàêaeå õàðàêòåðíî äëÿ ãèïîê-ñè÷åñêè-èøåìè÷åñêèõ è òðàâìàòè÷åñêèõ ïîâðåaeäå-íèé, ñòðåññà, íåéðîäåãåíåðàòèâíûõ çàáîëåâàíèé, òîê-ñè÷åñêèõ âîçäåéñòâèé, ôåíîìåíà ýêñàéòîòîêñè÷íîñòè, íàðóøåíèé ðàçâèòèÿ ãîëîâíîãî ìîçãà [19,56,70]. Ýòî îáóñëîâëåíî òåì, ÷òî íåçàâèñèìî îò ïåðâè÷íîãî âîç-äåéñòâèÿ ïðîèñõîäèò àêòèâàöèÿ îñíîâíûõ ýôôåêòîð-íûõ êëåòîê -ìèêðîãëèè è àñòðîöèòîâ (ðåàêòèâíûé ãëèîç), èíäóêöèÿ ýêñïðåññèè ãåíîâ, îïðåäåëÿþùèõ îò-âåò êëåòêè íà äåéñòâèå ïîâðåaeäàþùåãî ôàêòîðà, ïðî-äóêöèÿ ìîëåêóë ñ ïðî-èëè ïðîòèâîâîñïàëèòåëüíîé àê-òèâíîñòüþ, ðåàëèçóþòñÿ ìåõàíèçìû èììóííîãî îòâå-òà.…”