A neurovascular niche for neurogenesis after stroke
A neurovascular niche for neurogenesis after stroke
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DOI：
10.1523/jneurosci.4323-06.2006
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发表时间：
2006-12-13
影响因子：
5.3
通讯作者：
Carmichael, S. Thomas
中科院分区：
文献类型：
--
作者：
Ohab, John J.;Fleming, Sheila;Carmichael, S. Thomas
中风导致细胞死亡，但也会在缺血性损伤部位产生和迁移新的神经元。中风后诱导神经元再生和迁移的细胞环境尚未确定。我们已经使用了一个模型的长距离迁移的新生神经元从脑室下区皮质中风后，以确定细胞的线索，诱导中枢神经系统损伤后的神经元再生。有丝分裂，遗传和病毒标记和趋化因子/生长因子获得和功能丧失的研究表明，中风诱导神经发生从GFAP表达的祖细胞在脑室下区和迁移的新生神经元到一个独特的神经血管生态位在梗死周围皮层。在这个神经血管龛内，新生的未成熟神经元与重塑的血管系统密切相关。神经发生和血管生成通过基质衍生因子1（SDF 1）和血管生成素1（Ang 1）的血管生成而因果联系。此外，SDF 1和Ang 1促进卒中后神经母细胞迁移和行为恢复。这些实验定义了中风后神经元再生的新脑环境，并确定了脑损伤功能恢复期间血管生成和神经发生之间共享的分子机制。
Stroke causes cell death but also birth and migration of new neurons within sites of ischemic damage. The cellular environment that induces neuronal regeneration and migration after stroke has not been defined. We have used a model of long-distance migration of newly born neurons from the subventricular zone to cortex after stroke to define the cellular cues that induce neuronal regeneration after CNS injury. Mitotic, genetic, and viral labeling and chemokine/growth factor gain- and loss-of-function studies show that stroke induces neurogenesis from a GFAP-expressing progenitor cell in the subventricular zone and migration of newly born neurons into a unique neurovascular niche in peri-infarct cortex. Within this neurovascular niche, newly born, immature neurons closely associate with the remodeling vasculature. Neurogenesis and angiogenesis are causally linked through vascular production of stromal-derived factor 1 (SDF1) and angiopoietin 1 (Ang1). Furthermore, SDF1 and Ang1 promote post-stroke neuroblast migration and behavioral recovery. These experiments define a novel brain environment for neuronal regeneration after stroke and identify molecular mechanisms that are shared between angiogenesis and neurogenesis during functional recovery from brain injury.