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

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 资助的中心拨款提供的资源的众多研究子项目之一。子项目和研究者 (PI) 可能已从另一个 NIH 来源获得主要资金，因此可以在其他 CRISP 条目中出现。列出的机构是中心的机构，不一定是研究者的机构。拟议的研究反映了博士实验室之间的跨学科合作。麦克尼尔、琼斯和沙勒特将进一步了解神经可塑性与促进脑损伤后功能恢复的治疗策略之间的协同作用背后的细胞和分子事件。该实验设计融合了麦克尼尔实验室与琼斯和沙勒特实验室在神经可塑性细胞机制方面的研究专业知识，琼斯和沙勒特研究了行为经验对缺血性脑损伤后神经可塑性和功能恢复的影响。该研究的目的是确定康复训练是否可以增强神经突的生长和参与反应性突触发生的候选分子的基因表达，并确定可以作为开发中风康复新方法和创新方法的重点的关键分子。这项研究的基本原理是基于研究人员实验室以及其他人的先前研究，这些研究报告称：1）神经可塑性在缺血性脑损伤后的功能恢复中发挥着关键作用，2）康复性训练可以增强中风后功能的恢复，3）脑损伤后的皮质重组和突触替换涉及对特定病灶特异性生长相关蛋白、神经递质和神经营养蛋白组的差异调节，以及4）黑质纹状体神经元含有多巴胺和脑源性神经营养因子（BDNF），这是一种对神经元存活和突触功能至关重要的分子，对于脑损伤后维持纹状体目标神经元上的皮质纹状体突触至关重要。要测试的总体假设是：1）辅助使用康复训练可以增强已知调节皮层和纹状体神经元中神经突生长和棘密度的分子的上调； 2) 这些干预措施集中在与单胺激活和 BDNF 上调相关的细胞内信号通路上，从而发挥治疗作用。