The contributions of motor learning and inhibitory balance to stroke recovery

运动学习和抑制平衡对中风恢复的贡献

• 批准号: 9129768
• 负责人: STEVEN R ZEILER
• 金额: $ 18.93万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-15 至 2018-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9129768
• 关键词: Address; Adult; Affect; Animal Model; Animals; Area; Behavioral; Caring; Data; Development; Development Plans; Dose; Equilibrium; Fluorescence Microscopy; Fluoxetine; Foundations; Funding; Genetic; Genetic Models; Genetically Engineered Mouse; Goals; Health; Hour; Human; Immunofluorescence Immunologic; In Vitro; Interneurons; Intervention; Ion Channel; Ischemic Stroke; Laboratories; Learning; Leg; Light; Long-Term Care; Medial; Mediating; Medicine; Mentors; Motor; Mus; Neuronal Plasticity; Neurons; Parvalbumins; Patients; Positioning Attribute; Professional Competence; Property; Publishing; Recovery; Rehabilitation therapy; Research; Research Personnel; Role; Saline; Stroke; Techniques; Technology; Testing; Therapeutic; Time; Training; Training Programs; Translational Research; Wild Type Mouse; Work; acute stroke; arm; awake; calbindin; calretinin; career development; clinically relevant; cranium; design; disability; human data; in vivo; innovation; interest; knowledge base; motor impairment; motor learning; motor recovery; mouse model; neurotransmission; novel strategies; optogenetics; post stroke; programs; research and development; statistics; stroke recovery; stroke rehabilitation; stroke survivor

DESCRIPTION (provided by applicant): My proposal describes a mentored research and career development plan designed to facilitate my transition to an independent clinician-researcher. During the proposed 5 year plan, I will 1) characterize and begin to mechanistically define a post-stroke period of time during which motor recovery is decreasingly sensitive to motor training and 2) develop my career, skills, and knowledge base as I address this interesting and clinically relevant problem. Notably in human patients, most recovery from motor impairment after stroke occurs in the first month and is currently not the focus of most rehabilitation that predominantly targets function through compensatory strategies. Animal models, which also show the existence of a period of heightened recovery early after stroke, provide the opportunity to test approaches to augment and prolong this period of heightened recovery. Using a mouse model of post-stroke motor recovery, I propose to further define the post-stroke sensitive period by describing how the timing and dose of motor retraining interact to affect motor recovery, how fluoxetine (a commonly used anti-depressant medicine) can modify the sensitive period, and how specific neuronal activity influences this sensitive period. Specific training goals include 1) further development of mouse models in which to study post-stroke recovery, 2) developing a foundation in behavioral statistics, 3) learning advanced fluorescence microscopy, 4) learning in vivo optogenetics (optically controlling neuronal activity in an awake, behaving mouse), 5) translational research strategies, 6) developing an independent program of post-stroke recovery research, and 7) how to obtain independent funding. There is an urgent need to develop innovative approaches to post-stroke rehabilitation because despite improvements in acute stroke care, up to sixty percent of stroke survivors suffer disability in arm or leg use and up to one-third need placement in a longer term care facility. The training program and mentoring team that I have assembled will help to elucidate important recovery interventions, position me to exploit genetic models that impact neural plasticity, and use cutting edge technology to advance this work as I transition to my independent laboratory.

描述（由申请人提供）：我的建议描述了一项指导的研究和职业发展计划，旨在促进我向独立的临床医生研究员的过渡。在拟议的5年计划中，我将1）表征并开始机理定义势头后的时间，在此期间，当我解决这个有趣且与临床相关的问题时，运动恢复对运动训练的敏感性非常敏感； 2）发展我的职业，技能和知识基础。值得注意的是，在人类患者中，大多数从中风后的运动障碍中恢复到了第一个月，目前并不是大多数康复的重点，主要通过补偿策略将主要针对的作用。动物模型也表明了中风后早期恢复的一段时期的存在，这为测试方法提供了增强和延长这一恢复时期的机会。我建议使用势力后运动恢复的鼠标模型，以描述运动重新培训的时间和剂量如何相互作用以影响运动恢复，氟西汀（常用抗抑郁药）如何修改敏感周期以及特定的神经活性如何影响这一敏感的时期，以进一步定义触摸后敏感周期。具体的 培训目标包括1）进一步开发鼠标模型，在其中研究势后恢复，2）在行为统计中培养基础，3）学习高级荧光显微镜，4）在体内学习遗传学中学习（在清醒中的光学控制神经元活动，行为鼠标，5），5）5），5）5），5），6）6）转化后的研究策略，以开发造成后的研究后恢复后的独立研究，并独立于7）。迫切需要开发创新的中风后康复方法，因为尽管急性中风护理的改善，但高达60％的中风幸存者的手臂残疾 或使用腿部和最多三分之一的需求在长期护理设施中。我组装的培训计划和指导团队将有助于阐明重要的恢复干预措施，使我利用影响神经可塑性的遗传模型并使用切割 当我过渡到独立实验室时，边缘技术可以推进这项工作。