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资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心机构，不一定为研究者机构。这项拟议的研究反映了麦克尼尔，琼斯和Sjuert博士实验室之间的跨学科合作，这将进一步加深我们对神经可塑性和促进脑损伤后功能恢复的治疗策略之间协同作用的细胞和分子事件的理解。实验设计整合了来自McNeill实验室的神经可塑性细胞机制的研究专业知识，以及Jones和Sauffert的研究专业知识，他们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，并确定关键分子，这些分子可以作为中风康复新方法和创新方法的重点。该研究的基本原理是基于先前的研究，从制药商的实验室，以及那些其他人，谁报告说：1）神经可塑性在缺血性脑损伤后功能恢复中起关键作用，2）康复训练可促进脑卒中后功能恢复，3）脑损伤后的皮质重组和突触替代涉及病变特异性的生长相关蛋白、神经递质和神经营养因子的特异性组的差异调节，和4）含有多巴胺和脑源性神经营养因子（BDNF）（神经元存活和突触功能所必需的分子）的黑质纹状体神经元对于脑损伤后纹状体靶神经元上皮质纹状体突触的维持是必需的。要测试的首要假设是：1）康复训练的连续使用增强了已知调节皮质和纹状体神经元中的神经突生长和棘密度的分子的上调;以及2）这些干预会聚在与单胺激活和BDNF上调相关的细胞内信号通路上以获得其治疗效果。