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: 10364659
• 负责人: KENNETH B BAKER
• 金额: $ 43.5万
• 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 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10364659
• 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; 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; therapeutically effective; translational goal; 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.

项目总结/文摘