CELLULAR MECHANISMS OF NEUROPLASTICITY IN STROKE NEUROREHABILITATION

中风神经康复中神经可塑性的细胞机制

• 批准号: 7382212
• 负责人: THOMAS Hugh MCNEILL
• 金额: $ 8.8万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-08-01 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7382212
• 关键词: CELLULAR; MECHANISMS; NEUROPLASTICITY; STROKE; NEUROREHABILITATION; CELLULAR; MECHANISMS; NEUROPLASTICITY; STROKE; NEUROREHABILITATION

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. The proposed study reflects the interdisciplinary collaboration between the laboratories of Drs. McNeill, Jones and Schallert that will further our understanding of the cellular and molecular events underlying the synergism between neural plasticity and treatment strategies that promote the recovery of function after brain damage. The experimental design integrates the research expertise on the cellular mechanism of neural plasticity from McNeill''s laboratory with that of Jones and Schallert, who have examined the influence of behavioral experience on neural plasticity and recovery of function after ischemic brain injury. The goal of the study is to determine whether rehabilitative training can enhance neurite outgrowth and gene expression of candidate molecules involved in reactive synaptogenesis and identify key molecules that can serve as the focus for the development of new and innovative approaches in stroke rehabilitation. The rationale for the study is based on previous studies from the investigators'' laboratories, as well as those of others, who have reported that: 1) neural plasticity plays a critical role in the recovery of function after ischemic brain injury, 2) rehabilitative training can enhance the recovery of function after stroke, 3) cortical reorganization and synapse replacement after brain injury involves the differential regulation of specific sets of growth-associated proteins, neurotransmitters and neurotrophins that are lesion-specific, and 4) nigrostriatal neurons that contain both dopamine and brain-derived neurotrophic factor (BDNF), a molecule essential to neuron survival and synapse function, are essential for the maintenance of corticostriatal synapses on striatal target neurons after brain injury. The overarching hypotheses to be tested are: 1) that adjunctive use of rehabilitative training enhances the upregulation of molecules known to modulate neurite outgrowth and spine density in neurons of the cortex and striatum; and 2), that these interventions converge on intracellular siqnaling pathways associated with monoamine activation and BDNF upregulation for their therapeutic effect.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构适用于该中心，这不一定是调查员的机构。拟议的研究反映了DRS实验室之间的跨学科合作。 McNeill，Jones和Schallert将进一​​步了解我们对神经可塑性与治疗策略之间协同作用的细胞和分子事件的理解，这些事件促进了脑损伤后功能的恢复。实验设计将麦克尼尔（McNeill）实验室神经可塑性细胞可塑性的细胞机制的研究专业知识与琼斯（Jones）和夏勒特（Schallert）的实验室结合在一起，后者研究了行为经验对缺血性脑损伤后功能的影响和功能恢复的影响。该研究的目的是确定康复训练是否可以增强参与反应性突触发生的候选分子的神经突生长和基因表达，并确定可以作为中风康复中新的和创新方法的重点的关键分子。该研究的理由是基于研究者的实验室以及其他报告的研究，他们报告说：1）神经可塑性在缺血性脑损伤后的功能恢复中起着至关重要具有病变特异性的神经递质和神经营养蛋白，以及4）含有多巴胺和脑衍生的神经营养因子（BDNF）的NigroStriatal神经元（BDNF），这是神经元存活和突触功能所必需的分子，对于维持皮层促进型脑层造成脑层造成肿瘤后，是必不可少的。要测试的总体假设是：1）辅助使用康复训练增强了已知可调节神经突生长和脊柱密度的分子的上调；和2），这些干预措施会在与单胺激活和BDNF上调有关的细胞内siqnaling途径上汇聚，以表彰其治疗作用。