The Role of Endogenous Neurogenesis in Functional Recovery and Motor Map Reorganization Induced by Rehabilitative Therapy after Stroke in Rats

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• 作者：Takashi Shiromoto ; MD^* ; ^&dagger ; ; Naohiko Okabe ; PhD^* ; ^{n-okabe@med.kawasaki-m.ac.jp} ; Feng Lu ; PhD^* ; Emi Maruyama-Nakamura ; PhD^* ; Naoyuki Himi ; PhD^* ; Kazuhiko Narita ; PhD^* ; Yoshiki Yagita ; MD^&dagger ; ; Kazumi Kimura ; MD^&Dagger ; ; Osamu Miyamoto ; MD^*
• 关键词：Cerebral ischemia ; endogenous neurogenesis ; motor map reorganization ; motor recovery ; rehabilitative therapy ; cytosine-β-d-arabinofuranoside (Ara-C)
• 刊名：Journal of Stroke and Cerebrovascular Diseases
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：26
• 期：2
• 页码：260-272
• 全文大小：3677 K
• 卷排序：26

文摘

Endogenous neurogenesis is associated with functional recovery after stroke, but the roles it plays in such recovery processes are unknown. This study aims to clarify the roles of endogenous neurogenesis in functional recovery and motor map reorganization induced by rehabilitative therapy after stroke by using a rat model of cerebral ischemia (CI).MethodsIschemia was induced via photothrombosis in the caudal forelimb area of the rat cortex. First, we examined the effect of rehabilitative therapy on functional recovery and motor map reorganization, using the skilled forelimb reaching test and intracortical microstimulation. Next, using the same approaches, we examined how motor map reorganization changed when endogenous neurogenesis after stroke was inhibited by cytosine-β-d-arabinofuranoside (Ara-C).ResultsRehabilitative therapy for 4 weeks after the induction of stroke significantly improved functional recovery and expanded the rostral forelimb area (RFA). Intraventricular Ara-C administration for 4-10 days after stroke significantly suppressed endogenous neurogenesis compared to vehicle, but did not appear to influence non-neural cells (e.g., microglia, astrocytes, and vascular endothelial cells). Suppressing endogenous neurogenesis via Ara-C administration significantly inhibited (~50% less than vehicle) functional recovery and RFA expansion (~33% of vehicle) induced by rehabilitative therapy after CI.ConclusionsAfter CI, inhibition of endogenous neurogenesis suppressed both the functional and anatomical markers of rehabilitative therapy. These results suggest that endogenous neurogenesis contributes to functional recovery after CI related to rehabilitative therapy, possibly through its promotion of motor map reorganization, although other additional roles cannot be ruled out.