Ceanga Mihai, Dahab Mahmoud, Witte Otto W, Keiner Silke
Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.
Section Translational Neuroimmunology, Department of Neurology, Jena University Hospital, Jena, Germany.
Front Neurosci. 2021 Aug 10;15:700297. doi: 10.3389/fnins.2021.700297. eCollection 2021.
In the aftermath of an acute stroke, numerous signaling cascades that reshape the brain both in the perilesional zone as well as in more distal regions are activated. Despite continuous improvement in the acute treatment of stroke and the sustained research efforts into the pathophysiology of stroke, we critically lag in our integrated understanding of the delayed and chronic responses to ischemic injury. As such, the beneficial or maladaptive effect of some stroke-induced cellular responses is unclear, restricting the advancement of therapeutic strategies to target long-term complications. A prominent delayed effect of stroke is the robust increase in adult neurogenesis, which raises hopes for a regenerative strategy to counter neurological deficits in stroke survivors. In the adult brain, two regions are known to generate new neurons from endogenous stem cells: the subventricular zone (SVZ) and the dentate subgranular zone (SGZ) of the hippocampus. While both niches respond with an increase in neurogenesis post-stroke, there are significant regional differences in the ensuing stages of survival, migration, and maturation, which may differently influence functional outcome. External interventions such as rehabilitative training add a further layer of complexity by independently modulating the process of adult neurogenesis. In this review we summarize the current knowledge regarding the effects of ischemic stroke on neurogenesis in the SVZ and in the SGZ, and the influence of exogenous stimuli such as motor activity or enriched environment (EE). In addition, we discuss the contribution of SVZ or SGZ post-stroke neurogenesis to sensory, motor and cognitive recovery.
在急性中风后,许多重塑大脑的信号级联反应在病灶周围区域以及更远端区域被激活。尽管中风的急性治疗不断改进,对中风病理生理学的研究也持续进行,但我们在对缺血性损伤的延迟和慢性反应的综合理解方面仍严重滞后。因此,一些中风诱导的细胞反应的有益或适应不良作用尚不清楚,这限制了针对长期并发症的治疗策略的进展。中风的一个突出延迟效应是成年神经发生的强劲增加,这为对抗中风幸存者神经功能缺损的再生策略带来了希望。在成人大脑中,已知有两个区域可从内源性干细胞产生新神经元:脑室下区(SVZ)和海马齿状颗粒下区(SGZ)。虽然两个生态位在中风后神经发生都会增加,但在随后的存活、迁移和成熟阶段存在显著的区域差异,这可能对功能结果产生不同影响。诸如康复训练等外部干预通过独立调节成年神经发生过程增加了另一层复杂性。在本综述中,我们总结了关于缺血性中风对SVZ和SGZ神经发生的影响以及运动活动或丰富环境(EE)等外源性刺激的影响的现有知识。此外,我们讨论了中风后SVZ或SGZ神经发生对感觉、运动和认知恢复的贡献。