Cognitive Neurorehabilitation to Enhance Recovery After Stroke

认知神经康复促进中风后恢复

• 批准号: 7812111
• 负责人: DeAnna L Adkins
• 金额: $ 22.07万
• 依托单位: UNIVERSITY OF TEXAS AT AUSTIN
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-01 至 2012-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7812111
• 关键词: Acetylcholinesterase Inhibitors; Address; Animal Model; Animals; Area; Behavioral; Biological Assay; Biological Models; Biological Neural Networks; Brain; Brain Injuries; Brain region; Bromodeoxyuridine; Cell Maintenance; Cell Proliferation; Cells; Clinical Treatment; Cognitive; Complex; Coupling; Effectiveness; Endothelin-1; Episodic memory; Financial compensation; Foundations; Future; Golgi Apparatus; Hippocampus (Brain); Human; Impaired cognition; Impairment; Injection of therapeutic agent; Investigation; Ischemic Stroke; Knowledge; Laboratories; Learning; Memory; Middle Cerebral Artery Occlusion; Modeling; Motor; Motor Skills; Neurobiology; Neurologic; Neuronal Plasticity; Neurons; Neurorehabilitation; Peptides; Performance; Pharmacological Treatment; Pharmacotherapy; Phenotype; Process; Rattus; Recovery; Rehabilitation therapy; Research; Residual state; Rodent Model; Stroke; Synapses; Synaptic plasticity; Testing; Training; Treatment Efficacy; Vertebral column; Work; base; behavior measurement; cognitive function; cognitive recovery; cognitive rehabilitation; cognitive training; density; dentate gyrus; donepezil; improved; inhibitor/antagonist; light microscopy; memory process; middle cerebral artery; motor skill learning; nerve stem cell; neural circuit; neurogenesis; neuromechanism; post stroke; public health relevance; relating to nervous system; skill acquisition; stroke recovery; stroke rehabilitation

DESCRIPTION (provided by applicant): The main objective of these studies is to determine if cognitive neurorehabilitation improves memory and induces neural plasticity in residual brain areas following stroke. There is a well-established model system to examine rehabilitation-induced motor recovery and plasticity following experimental strokes in rats. Motor recovery is thought to be a process of "relearning" in which motor functions are reacquired through functional compensation within spared brain regions. Several laboratories have demonstrated that such functional compensation is supported by synaptic plasticity within residual neural circuits that is driven by rehabilitation. However, it is unknown whether cognitive neurorehabilitative training will improve cognitive performance, such as improved memory. It seems possible that focused cognitive neurorehabilitation would improve specific areas of cognitive function and induce greater neural adaptive changes in spared brain regions that are relevant to the rehabilitated cognitive function. However, basic neurobiology research suggests that the neural basis of motor skills acquisition and performance is different from cognitive tasks such as episodic memory. Motor skills and cognitive functions involve different neural networks and thus the requirements of learning- induced neural plasticity in these networks are also likely different. This proposal is to systematically investigate how cognitive rehabilitative therapy after ischemic insult can improve cognitive ability, including the neural bases of the improvements and the efficacy of combining rehabilitation with pharmacological treatments. This will be investigated in a rat model of stroke (middle cerebral artery occlusion) using a combination of sensitive behavioral measures and manipulations of cognitive function and assays of neuronal and synaptic structural plasticity in the hippocampus. The aims of this project are to test the hypotheses that: 1) Post-stroke training in tasks requiring episodic memory will improve performance on tests of cognitive ability in an animal model of stroke compared to non- trained groups; 2) Cognitive rehabilitative training that improves cognitive ability following stroke will result in restorative plasticity in the hippocampus compared to non-trained groups; 3) Coupling cognitive neurorehabilitative training with an acetylcholinesterase inhibitor will enhance the efficacy of post-stroke cognitive neurorehabilitation. These investigations are expected to elucidate mechanisms involved in cognitive recovery after brain injury, with the potential of leading to better clinical treatment approaches. PUBLIC HEALTH RELEVANCE: Currently, there is not a well-developed rodent model of cognitive neurorehabilitation following neurological insult. We propose to develop a rat model of cognitive neurorehabilitative training that will provide knowledge regarding the effectiveness of task specific cognitive training and the neural mechanisms underlying its therapeutic efficacy following stroke. These investigations will serve as a foundation to test adjunctive therapies to optimize recovery from stroke.

描述（由申请人提供）：这些研究的主要目的是确定认知神经康复是否改善记忆并诱导卒中后残留脑区的神经可塑性。有一个完善的模型系统来检查大鼠实验性中风后康复诱导的运动恢复和可塑性。运动恢复被认为是一个“再学习”的过程，其中运动功能通过备用脑区域内的功能补偿重新获得。几个实验室已经证明，这种功能补偿是由残余神经回路内的突触可塑性支持的，所述残余神经回路由康复驱动。然而，目前还不清楚认知神经康复训练是否会改善认知能力，例如改善记忆力。集中的认知神经康复似乎有可能改善认知功能的特定区域，并在与康复的认知功能相关的备用脑区引起更大的神经适应性变化。然而，基础神经生物学研究表明，运动技能获得和表现的神经基础与情景记忆等认知任务不同。运动技能和认知功能涉及不同的神经网络，因此这些网络中学习诱导的神经可塑性的要求也可能不同。本研究旨在系统地探讨缺血性脑损伤后认知康复治疗对认知功能的改善作用，包括认知功能改善的神经基础以及康复治疗与药物治疗相结合的疗效。这将在中风（大脑中动脉闭塞）的大鼠模型中使用敏感的行为测量和认知功能的操作以及海马中神经元和突触结构可塑性的测定的组合来研究。该项目的目的是检验以下假设：1）与未训练组相比，在需要情景记忆的任务中进行中风后训练将改善中风动物模型在认知能力测试中的表现; 2）与未训练组相比，改善中风后认知能力的认知康复训练将导致海马体的恢复性可塑性; 3）认知神经康复训练与乙酰胆碱酯酶抑制剂联合应用可提高脑卒中后认知神经康复的疗效。这些研究有望阐明脑损伤后认知恢复的机制，并有可能导致更好的临床治疗方法。公共卫生相关性：目前，神经损伤后认知神经康复的啮齿动物模型尚未开发。我们建议开发一种认知神经康复训练的大鼠模型，该模型将提供关于任务特异性认知训练的有效性及其在中风后的治疗功效的神经机制的知识。这些研究将作为基础，以测试预防性治疗，以优化中风的恢复。