MECHANISMS OF FUNCTIONAL AND BEHAVIORAL RECOVERY FOLLOWING ISCHEMIC STROKE

缺血性中风后功能和行为恢复的机制

• 批准号: 8700071
• 负责人: ADAM Q BAUER
• 金额: $ 15.12万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-04-01 至 2019-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8700071
• 关键词: Acute; Adult; American Heart Association; Animal Model; Behavior; Behavioral; Bilateral; Biological Markers; Biological Neural Networks; Brain; Brain Injuries; Brain region; Cause of Death; Chronic; Complex; Conflict (Psychology); Contralateral; Disease; Distant; Doctor of Philosophy; Equilibrium; Evolution; Exhibits; Functional Imaging; Future; Goals; Grant; Hand; Health; Human; Image; Incidence; Infarction; Injury; Interneurons; Ischemia; Ischemic Stroke; K-Series Research Career Programs; Learning; Lesion; Life; Lighting; Link; Magnetic Resonance Imaging; Measures; Mediating; Medical; Mentors; Mentorship; Modality; Movement; Mus; Neuronal Plasticity; Neurons; Neurosciences; Noise; Optics; Outcome; Patients; Pattern; Performance; Peripheral; Physics; Physiological; Process; Recovery; Recovery of Function; Rehabilitation therapy; Reporting; Research; Resolution; Role; Signal Transduction; Somatosensory Cortex; Stroke; Structure; Survivors; Technology; Testing; Therapeutic; Time; Training; Transcranial magnetic stimulation; United States; Universities; Washington; Wild Type Mouse; Work; base; behavior influence; brain repair; career; disability; effective therapy; experience; hippocampal pyramidal neuron; medical schools; mouse model; neuroimaging; new technology; optogenetics; prognostic; promoter; public health relevance; stroke recovery; therapy design

DESCRIPTION (provided by applicant): The goal of this K25 Mentored Career Development Award is to provide the candidate (a Ph.D. in experimental physics) with the necessary training in neuroscience, and mechanisms of brain injury and repair to launch an independent career studying stroke recovery. Washington University School of Medicine will provide an ideal setting for the candidate's training by providing them access to some of the leading medical and biomedical collaborators in the fields of brain function, functional imaging, stroke, and stroke recovery. The proposed research, which will be conducted under the co-mentorship of Drs. Jin-Moo Lee and Joseph Culver, will examine the role of network connectivity and perilesional activity on cortical plasticity and behavioral recovery using a mouse model of ischemic stroke. Current research suggests that complex behaviors rely on distributed network interaction; disruption in these neural networks, for example by stroke, has consequently been shown to alter brain function and behavioral outcome. However, what is much less clear is the impact of altered networks on behavioral and functional recovery after brain injury. There is accumulating evidence that physiological activity (through use of the impaired modality) enhances recovery; it follows that network connectivity in the brain (or lack of) may have profound influences on stroke recovery mechanisms. Understanding the implications of network structure and activity on stroke recovery, and then potential therapeutic approaches, will require mechanistic studies linking functional connectivity (fc) measures to network manipulations during the recovery period. Towards this goal, this grant proposes to take advantage of two novel technologies, functional connectivity optical intrinsic signal imaging (fcOIS, co-developed by the candidate), which for the first time allows fc imaging in mice, and ontogenetic. This proposal will test the hypothesis that chronic, intermittent activation or inhibition of local or distant brain circuits modulates network plasticity following focal ischemic injury through the following Aims: 1) Evaluate the time-course and evolution of network fc, functional remapping, and behavioral recovery following photothrombotic infarction of the forepaw somatosensory cortex (S1fp). 2) Determine the selective influence of perilesional inhibitory interneuronal activity on fc, remapping, and behavioral recovery after S1fp photothrombosis. 3) Determine the selective influence of contralesional homotopic input to perilesional cortex on fc, remapping and behavioral recovery after S1fp photothrombosis. Results from the proposed studies could have implications for the design of interventions to promote recovery following human stroke: either through direct non-invasive brain stimulation or through optimization of physiologic therapeutic maneuvers (e.g. "forced-use" therapies designed to enhance plasticity through stimulation of the brain's natural recovery mechanisms.

描述（由申请人提供）：这个K25指导职业发展奖的目标是为候选人（实验物理学博士学位）提供神经科学的必要培训，以及脑损伤和维修机制，以启动独立的职业研究中风恢复。华盛顿大学医学院将通过为候选人的培训提供理想的环境，通过为他们提供大脑功能，功能成像，中风和中风恢复领域的一些领先的医学和生物医学合作者。拟议的研究将在DR的同事下进行。 Jin-Moo Lee和Joseph Culver将使用缺血性中风的小鼠模型来研究网络连通性和周围活性对皮质可塑性和行为恢复的作用。当前的研究表明，复杂的行为依赖于分布式网络交互。因此，这些神经网络中的破坏，例如通过中风，已被证明会改变大脑功能和行为结果。但是，不清楚的是，改变网络对脑损伤后行为和功能恢复的影响。有积极的证据表明生理活性（通过使用受损的方式）增强了恢复。因此，大脑中的网络连通性（或缺乏）可能会对中风恢复机制产生深远的影响。了解网络结构和活动对中风恢复的含义，然后了解潜在的治疗方法，将需要在恢复期间将功能连通性（FC）措施与网络操作联系起来的机械研究。为了实现这一目标，该赠款提议利用两种新型技术，功能连通性光学固有信号成像（FCOI，由候选人共同开发），这是小鼠首次允许FC成像和遗传学。 This proposal will test the hypothesis that chronic, intermittent activation or inhibition of local or distant brain circuits modulates network plasticity following focal ischemic injury through the following Aims: 1) Evaluate the time-course and evolution of network fc, functional remapping, and behavioral recovery following photothrombotic infarction of the forepaw somatosensory cortex (S1fp). 2）确定S1FP光栓塞后的抑制性抑制性神经元活性对FC，重新映射和行为恢复的选择性影响。 3）确定对侧同位素对周围皮层对FC的选择性影响，S1FP光栓塞后重新映射和行为恢复。拟议研究的结果可能对设计干预措施的设计具有影响，以促进人类中风后的恢复：通过直接的非侵入性脑刺激或通过优化生理治疗手术（例如“强制使用”疗法，旨在通过刺激大脑的自然恢复机制来增强可塑性的疗法。