Local slow wave sleep in repair and recovery after stroke

局部慢波睡眠在中风后修复和恢复中的作用

• 批准号: 10474280
• 负责人: Eric C Landsness
• 金额: $ 18.86万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-08-01 至 2025-07-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10474280
• 关键词: Acute; Adult; Affect; Area; Award; Basic Science; Behavior; Behavioral; Blood Vessels; Brain; Brain Injuries; Brain Stem; Caring; Cell Nucleus; Clinical; Collaborations; Communities; Data; Development; Doctor of Philosophy; Electrophysiology (science); Engineering; Environment; Exhibits; Faculty; Future; Generations; Genetic; Goals; Health; Hour; Human; Hypothalamic structure; Image; Imaging Techniques; Incidence; Individual; Infarction; Injury; Interneurons; Ischemia; Ischemic Brain Injury; K-Series Research Career Programs; Knowledge; Lead; Learning; Long-Term Potentiation; Measures; Mediating; Mediator of activation protein; Memory; Mentors; Mentorship; Molecular; Monitor; Mus; Neocortex; Neurologist; Neuronal Injury; Neurons; Neurosciences; Optics; Outcome; Patients; Pharmacology; Physicians; Play; Process; Quality of life; Recovery; Recovery of Function; Rehabilitation therapy; Reproducibility; Research; Research Technics; Role; Scientist; Shapes; Sleep; Sleep Deprivation; Slow-Wave Sleep; Somatosensory Cortex; Speech; Stroke; Synapses; Synaptic plasticity; Testing; Thalamic structure; Therapeutic; Therapeutic Intervention; Time; Training; United States; Universities; Wakefulness; Washington; base; brain repair; career; career development; designer receptors exclusively activated by designer drugs; disability; effective intervention; experience; experimental study; fluorescence imaging; functional outcomes; imaging modality; improved; in vivo imaging; innovation; interest; molecular marker; mouse model; nervous system disorder; neural repair; neuroimaging; neuronal circuitry; novel therapeutic intervention; novel therapeutics; post stroke; release of sequestered calcium ion into cytoplasm; repaired; stroke model; stroke recovery; stroke survivor; success; synaptogenesis; targeted treatment; therapeutic target

The goal of this mentored career development award is to enable the candidate’s transition to independence as a physician-scientist studying the connection between plasticity, sleep and stroke. The candidate is an MD, PhD sleep neurologist with a background in engineering, human sleep electrophysiology and how it relates to brain plasticity. The award will help the candidate gain experience in basic genetic, molecular and in-vivo imaging techniques as well as an in-depth knowledge of the cellular and molecular mechanisms involved in plasticity mediated neuronal repair. This award will help the candidate to become an independent physician scientist using sleep as way to accelerate the pace of scientific discovery and its application to the care of individuals with neurological disease. This career development award brings together three experts covering the diverse fields of sleep (Landsness – PI), plasticity of brain recovery (Lee – Mentor) and optical neuroimaging (Culver – Mentor) to tackle this innovative concept and potentially open-up a new field of research. The research environment in which this career development award is proposed is outstanding. Dr. Jin Moo Lee, a translational neuroscientist and vascular neurologist with an interest in the plasticity of stroke recovery, has a long track record of both scientific and mentorship success. Dr. Joe Culver, is a long-time collaborator of the Lee lab and highly experienced in the imaging techniques the candidate will use. Finally, the Washington University neuroscience community emphasizes high quality research, career development of young faculty and collaboration, all keys to his success. An objective of this proposal is to understand the role of slow wave sleep (SWS) in repair and recovery after focal ischemic brain injury. Local SWS is critical for learning-related brain plasticity. Mechanisms involved in brain plasticity have been postulated to be necessary for successful neural repair and recovery after brain injury. Neuronal activity in somatostatinergic interneurons (SOMi) has recently been shown to critically mediate SWS. We propose to 1) determine the role of global SWS in a mouse model of brain repair following focal ischemia (photothrombosis) in somatosensory cortex and 2) locally manipulate SWS (via SOMi using chemogenetics) to determine if modulating local SWS affects cortical remapping, synaptogenesis, and sensorimotor recovery. If the hypothesis is correct, it will show that locally manipulating SWS can selectivity drive plasticity and ultimately recovery from stroke. It will also determine if SOMi might be amenable to targeting and may help shape a novel therapeutic approach to enhancing plasticity and recovery following stroke. This career development award is the ideal platform for the candidate to acquire important training in basic research techniques, deepen his understanding of the role SWS in repair and recovery of stroke, and will launch him towards an independent research career focused on using sleep to aid in care of individuals suffering from stroke.

这个指导职业发展奖的目标是使候选人的过渡到独立 作为一个研究可塑性、睡眠和中风之间联系的物理学家和科学家。候选人是医学博士， 睡眠神经学家博士，具有工程学背景，人类睡眠电生理学及其与 大脑可塑性该奖项将帮助候选人获得基础遗传，分子和体内的经验 成像技术以及对参与的细胞和分子机制的深入了解， 可塑性介导的神经元修复。该奖项将帮助候选人成为独立的医生 科学家利用睡眠作为加快科学发现步伐的方式，并将其应用于护理 患有神经系统疾病的人。这个职业发展奖汇集了三位专家， 不同领域的睡眠（Landsness-PI），大脑恢复的可塑性（Lee-Mentor）和光学神经成像 （卡尔弗-导师）来解决这个创新的概念，并可能开辟一个新的研究领域。研究 在这个职业发展奖提出的环境是杰出的。Jin Moo Lee博士，翻译 神经科学家和血管神经学家，对中风恢复的可塑性感兴趣，有很长的记录 科学和指导的成功。乔·卡尔弗博士是李实验室的长期合作者， 候选人将使用的成像技术经验丰富。最后，华盛顿大学的神经科学 社区强调高质量的研究，年轻教师的职业发展和合作，所有的关键 他的成功。 本提案的目的是了解慢波睡眠（SWS）在脑损伤后的修复和恢复中的作用。 局部缺血性脑损伤局部SWS对学习相关的大脑可塑性至关重要。中涉及的机制 脑可塑性被认为是脑损伤后成功的神经修复和恢复所必需的。 生长抑素能中间神经元（SOMi）的神经元活动最近已被证明是重要的介导SWS。 我们建议：1）确定整体SWS在小鼠局灶性脑缺血后脑修复模型中的作用 （光血栓形成）和2）局部操纵SWS（通过SOMi使用化学遗传学）， 确定调节局部SWS是否影响皮质重映射、突触发生和感觉运动恢复。 如果假设是正确的，它将表明，局部操纵SWS可以选择性地驱动可塑性， 最终从中风中恢复。它还将确定SOMi是否可以成为目标，并可能有助于 形成一种新的治疗方法，以提高可塑性和恢复中风后。这个职业 发展奖是候选人获得基础研究重要培训的理想平台 技术，加深他对SWS在中风修复和恢复中的作用的理解，并将启动他 走向一个独立的研究生涯，专注于使用睡眠来帮助照顾中风患者。