State Key Laboratory of Natural Medicines, Department of Physiology, China Pharmaceutical University, Nanjing 210009, China.
Brain Res Bull. 2020 Nov;164:1-13. doi: 10.1016/j.brainresbull.2020.07.005. Epub 2020 Aug 5.
Neurogenesis process in the chronic phase of ischemic stroke has become the focus of research on stroke treatment recently, mainly through the activation of related pathways to increase the differentiation of neural stem cells (NSCs) in the brain sub-ventricular zone (SVZ) and subgranular zone (SGZ) of hippocampal dentate gyrus (DG) areas into neurons, promoting neurogenesis. While there is still debate about the longevity of active adult neurogenesis in humans, the SVZ and SGZ have the capacity to upregulate neurogenesis in response to cerebral ischemia, which opens discussion about potential treatment strategies to harness this neuronal regenerative response. Wnt signaling pathway is one of the most important approaches potentially targeting on neurogenesis after cerebral ischemia, appropriate activation of which in NSCs may help to improve the sequelae of cerebral ischemia. Various therapeutic approaches are explored on preclinical stage to target endogenous neurogenesis induced by Wnt signaling after stroke onset. This article describes the composition of Wnt signaling pathway and the process of neurogenesis after cerebral ischemia, and emphatically introduces the recent studies on the mechanisms of this pathway for post-stroke neurogenesis and the therapeutic possibility of activating the pathway to improve neurogenesis after stroke.
在缺血性脑卒中的慢性期,神经发生过程已成为脑卒中治疗研究的焦点,主要通过激活相关途径,增加脑侧脑室下区(SVZ)和海马齿状回颗粒下区(SGZ)中的神经干细胞(NSCs)向神经元的分化,促进神经发生。虽然成人活跃性神经发生在人类中的持久性仍存在争议,但 SVZ 和 SGZ 有能力响应脑缺血上调神经发生,这引发了关于利用这种神经元再生反应的潜在治疗策略的讨论。Wnt 信号通路是脑缺血后潜在靶向神经发生的最重要方法之一,适当激活 NSCs 中的 Wnt 信号可能有助于改善脑缺血的后遗症。目前正在临床前阶段探索各种治疗方法,以针对脑卒中后 Wnt 信号诱导的内源性神经发生。本文描述了 Wnt 信号通路的组成和脑缺血后的神经发生过程,重点介绍了该通路促进脑卒中后神经发生的机制及其激活该通路改善脑卒中后神经发生的治疗可能性的最新研究。