NEURAL REPAIR AFTER STROKE

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 中风是成人残疾的主要原因。中风诱导神经干细胞/前体反应：新生的未成熟神经元（神经母细胞）迁移到损伤区域并分化为更成熟的神经元。这种脑卒中后的神经母细胞反应，如果得到适当的利用，可能会提供一种细胞替代的策略。本申请的目的是确定刺激成神经细胞迁移和定位到中风后脑中的梗死周围组织的细胞信号。神经元分化通常发生在成人中，与血管内皮细胞密切相关，称为神经血管龛的环境。中风引起梗塞周围血管系统的深刻变化。这项应用将建立在初步的数据，表明新出生的神经母细胞形成一个紧密的空间关系与血管内皮细胞在梗死周围的皮层，以测试中风诱导神经母细胞迁移和本地化的假设，通过创建一个新的神经血管环境或周围的梗死壁龛。参照血管生长因子和细胞引导分子，通过激光捕获成神经细胞及其相关的内皮细胞，将鉴定该生态位中成神经细胞和内皮细胞之间的结合信号分子。这些信号系统的功能获得和丧失实验将被用来确定它们在中风后神经发生中的机制作用。初步数据显示，全身施用候选血管生长因子及其拮抗剂通过梗塞周围皮质中开放的血脑屏障选择性地增加或减少中风后神经发生。这种选择性增强或减少卒中后神经发生的能力将用于确定卒中后新生神经元的长期存活和整合程度，以及卒中后神经发生对行为恢复的影响。总而言之，这个应用程序将应用机械实验，以确定分子信号，解剖组织和恢复的一个新的细胞环境修复中风后的影响？支持梗死周围皮质神经发生的神经血管小生境。与公共卫生的相关性：这些研究将确定中风后神经干细胞反应的机制，在中风损伤导致细胞丢失的区域提供新的神经元。对中风后促进这种神经干细胞反应的分子的理解将有助于开发新的疗法，以促进这种疾病中脑细胞的替代。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Stroke is the leading cause of adult disability. Stroke induces a neural stem cell/ precursor response: newly born, immature neurons (neuroblasts) migrate to the area of injury and differentiate into more mature neurons. This neuroblast response after stroke may offer a strategy of cell replacement if properly harnessed. The goal of this application is to define the cellular signals that stimulate neuroblast migration and localization to peri-infarct tissue in the brain after stroke. Neuronal differentiation normally occurs in the adult in close association with vascular endothelial cells, an environment termed the neurovascular niche. Stroke induces profound changes in the vasculature around the infarct. This application will build on preliminary data that shows that newly born neuroblasts form a tight spatial relationship with the vascular endothelium in peri-infarct cortex, to test the hypothesis that stroke induces neuroblast migration and localization by creating a novel neurovascular environment or niche surrounding the infarct. The conjoint signaling molecules between neuroblasts and endothelial cells in this niche will be identified, with reference to vascular growth factors and cell guidance molecules, by laser capture of neuroblasts and their associated endothelial cells. Gain and loss of function experiments within these signaling systems will then be used to identify their mechanistic roles in post-stroke neurogenesis. Preliminary data shows that systemic administration of candidate vascular growth factors and their antagonists selectively increase or decrease post-stroke neurogenesis, through an opened blood brain barrier in peri-infarct cortex. This ability to selectively augment or diminish post-stroke neurogenesis will be used to determine the long-term survival and degree of integration of newly born neurons after stroke, and the effect of post-stroke neurogenesis on behavioral recovery. Altogether, this application will apply mechanistic experiments to define the molecular signaling, anatomical organization and effect on recovery of a novel cellular environment for repair after stroke?a neurovascular niche that supports neurogenesis in peri-infarct cortex. Relevance to Public Health: These studies will define the mechanisms of a neural stem cell response after stroke, which provides new neurons in areas in which cells have been lost from stroke damage. An understanding of the molecules that promote this neural stem cell response after stroke will help develop novel therapies to promote replacement of brain cells in this disease.