Augmentation of Neurogenesis and Recovery After Stroke

超出所提供的空间。本研究计划的总体目标是确定药物和行为干预是否刺激成年大鼠中风后的神经发生和改善功能恢复。神经干细胞在成年哺乳动物大脑中的持续存在以及损伤刺激前脑神经发生的证据表明，内源性祖细胞是脑损伤或神经变性后神经元替代的来源。我们最近发现局灶性缺血增加成年大鼠心室下区（SVZ）的神经发生。一些SVZ神经母细胞分化为受损纹状体中的神经元，这些新细胞在中风后至少存在5周，并表达适合新纹状体神经元的表型标记。然而，更多到达受损纹状体的神经母细胞却无法存活。最近的研究也表明，行为操纵影响成人神经发生和中风后的恢复，但不知道这些过程是否相关。本研究的主要假设是增加新纹状体神经发生将促进成年大鼠中风后感觉运动功能的恢复。具体的假设是：1)生长/分化因子或星形胶质细胞来源的线索会刺激完整svz -嗅球通路的神经发生，并增加中风后纹状体神经发生（目的1和2）；2)神经发生是药物或康复干预诱导中风后功能恢复的主要因素（目的2和3）；3)生长/分化因子治疗与运动训练相结合比单独治疗更能促进脑卒中后神经发生和改善功能。(4)目标。具体目的是：t)确定特定的生长分化因子或星形胶质细胞来源的线索是否刺激前脑SVZ神经母细胞的增殖或分化；2)通过纹状体神经发生，确定用特定的有丝分裂因子和分化因子治疗是否会增强成年大鼠脑卒中后的功能恢复；3)研究刺激受损肢体运动活动的行为干预是否会提高脑卒中后神经母细胞的存活率和功能恢复，以及4)确定生长分化因子治疗和行为治疗联合治疗是否比单独治疗更能提高脑卒中后神经发生或功能结局。这些目标的进展将促进我们对脑损伤后神经干细胞调节和康复可塑性机制的理解，并可能导致新的中风再生疗法。网站性能 ======================================== 节结束 ===========================================

EXCEED THE SPACE PROVIDED. The overall goal of this research plan is to determine whether pharmacological and behavioral interventions stimulate neurogenesis and improve functional recovery after stroke in the adult rat. The persistence of neural stem cells in the adult mammalian brain and evidence that injury stimulates forebrain neurogenesis suggest that endogenous progenitors are a source for neuronal replacement after brain insults or neurodegeneration. We have recently discovered that focal ischemia increases neurogenesis in the adult rat subventricular zone (SVZ). Some SVZ neuroblasts differentiate into neurons in the injured striatum, and these new cells persist for at least 5 weeks after stroke and express phenotypic markers appropriate for neostriatal neurons. Many more neuroblasts that reach the injured striatum, however, fail to survive. Recent work also suggests that behavioral manipulations influence both adult neurogenesis and recovery from stroke, but it is not known whether these processes are linked. The main hypothesis of this proposal is that augmenting neostriatal neurogenesis will improve recovery of sensorimotor function after stroke in the adult rat. The specific hypotheses are: 1) growth/differentiation factors or astrocyte-derived cues will stimulate neurogenesis in the intact SVZ-olfactory bulb pathway, and increase striatal neurogenesis after stroke (Aims 1 and 2); 2) neurogenesis is a major factor in the functional recovery after stroke induced by pharmacological or rehabilitative interventions (Aims 2 and 3); 3) combining growth/differentiation factor treatment and motor training will increase neurogenesis and improve function after stroke more than either treatment alone. (Aim 4). The specific aims are: t) To determine whether specific growthdifferentiation factors or astrocyte-derived cues stimulate the proliferation or differentiation of forebrain SVZ neuroblasts; 2) To determine whether treatment with specific mitogenic and differentiation factors will augment, via striatal neurogenesis, functional recovery after stroke in the adult rat; 3) To investigate whether behavioral interventions to stimulate motor activity in the impaired limbs will enhance neuroblast survival and functional recovery after stroke," and 4) To determine whether combined growthdifferentiation factor treatment and behavioral therapy enhance neurogenesis or fimctional outcome after stroke more than either treatment alone. Progress in these aims will advance our understanding of mechanisms underlying neural stem cell regulation and rehabilitative plasticity after brain injury, and may lead to novel regenerative therapies for stroke. PERFORMANCE SITE ========================================Section End===========================================