Cerebellar deep brain stimulation to enhance chronic post-stroke rehabilitation

小脑深部脑刺激可增强慢性中风后康复

• 批准号: 9892037
• 负责人: KENNETH B BAKER
• 金额: $ 52.29万
• 依托单位: CLEVELAND CLINIC LERNER COM-CWRU
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-03-01 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892037
• 关键词: Address; Aftercare; Age; Anatomy; Animals; Area; BRAIN initiative; Behavioral; Cerebellar Nuclei; Cerebral cortex; Cerebrum; Chronic; Clinical; Collaborations; Corpus striatum structure; Coupling; Data; Deep Brain Stimulation; Dentate nucleus; Development; Disease; Electric Stimulation; Ensure; Epidemiology; Event; FDA approved; Family; Frequencies; Future; Glutamates; Goals; Human; Individual; Industrialization; Industry; Infarction; Ischemia; Ischemic Stroke; Knowledge; Lateral; Length; Long-Term Potentiation; Mediating; Mission; Modeling; Motor; Movement; National Institute of Neurological Disorders and Stroke; Nature; Neocortex; Neurons; Outcome; Output; Pathway interactions; Patient Selection; Patients; Pattern; Phase; Physiological; Public Health; Pulse Rates; Pyramidal Cells; Recommendation; Rehabilitation therapy; Research; Rodent; Rodent Model; Role; Severities; Sex Differences; Signal Transduction; Societies; Stroke; Structure; Synapses; System; Technology; Thalamic structure; Therapeutic; Therapeutic Intervention; Time; Translations; Treatment Efficacy; Upper Extremity; Work; active method; age group; base; cohort; daily functioning; density; design; disability; experimental study; hemiparesis; improved; interest; male; motor deficit; motor function recovery; motor impairment; motor recovery; motor rehabilitation; neurorestoration; novel; novel strategies; patient expectation; phase I trial; post stroke; pre-clinical; relating to nervous system; safety and feasibility; stroke patient; stroke recovery; stroke rehabilitation; stroke therapy; synaptogenesis; treatment response; white matter

PROJECT SUMMARY/ABSTRACT Stroke is a disease of epidemiological proportions in the industrialized world and is a leading cause of long- term disability. Half of all stroke patients suffer long-term motor deficits severe enough to be disabling despite contemporary rehabilitative efforts, which underscores the need for novel, neurorestorative therapies to enhance post-stroke motor recovery. We have previously proposed dentate nucleus deep brain stimulation (DN-DBS) as a therapy to facilitate motor recovery for patients with chronic upper extremity hemiparesis due to ischemic stroke. Our working hypothesis is that low-frequency DN-DBS augments excitatory dentatothalamocortical output, thereby enhancing cerebral cortical excitability, facilitating functional reorganization in perilesional cortical areas and further supporting motor recovery. Using a rodent model of ischemia, we have demonstrated that chronic stimulation can facilitate motor recovery and that the improvements are accompanied by sustained increments in excitability, reorganization of motor representation, and increased expression of markers of long-term potentiation and synaptogenesis in perilesional regions of the cerebral cortex. The experiments proposed in the present study will help to ensure successful human translation of this promising novel treatment while also systematically examining its mechanistic underpinnings. Specifically, the proposed experiments are designed to determine: a) how the anatomical extent and distribution of the ischemic core influences both treatment efficacy and carry-over of benefits; b) how movement-related, synchronized oscillatory activity across deep cerebellar nuclei and neocortex changes post-stroke and as a result of DN-DBS treatment and whether that activity could serve as a control signal in a paired-associative (closed-loop) treatment paradigm; c) whether age at the time of infarct negatively impacts therapeutic efficacy; and d) the anatomical and functional mechanisms underlying DN- DBS-enhanced motor rehabilitation. These studies will be performed by an investigative team with multiple long-standing collaborations aimed towards the development of DN-DBS technologies for the treatment of motor impairments following stroke.

项目摘要/摘要 中风是工业化世界中流行病学比例的疾病，是长期的主要原因 术语残疾。所有中风患者中有一半遭受长期的运动缺陷，尽管 当代康复努力，强调了对新颖的神经训练疗法的需求 增强冲程后运动恢复。我们以前提出了齿状核深脑刺激 （DN-DBS）作为一种疗法，可促进慢性上肢偏瘫患者的运动恢复 缺血性中风。我们的工作假设是低频DN-DBS增强兴奋性 齿状甲状腺皮质输出，从而增强脑皮质兴奋性，促进功能 在周围皮质区域进行重组，并进一步支持运动恢复。使用啮齿动物模型 缺血，我们已经证明了慢性刺激可以促进运动恢复，并且 改进伴随着兴奋性的持续增量，电动机的重组 表示长期增强和突触发生的标志物的表达增加 大脑皮质的周围区域。本研究中提出的实验将有助于确保 成功的人类翻译对这种有前途的新颖疗法，同时也系统地检查了它 机械基础。具体而言，提出的实验旨在确定：a） 缺血核心的解剖学范围和分布都会影响治疗疗效和承认 好处; b）在深小脑核和 新皮质在震动后改变，并且由于DN-DBS治疗以及该活动是否可以作为 配对缔合（闭环）处理范式中的对照信号； c）是否在梗塞时年龄 负面影响治疗功效； d）DN-的解剖学和功能机制 DBS增强运动康复。这些研究将由多个调查团队进行 长期合作旨在开发DN-DBS技术以治疗 中风后运动障碍。