Effects of Cortical Stimulation on Motor Recovery

皮质刺激对运动恢复的影响

• 批准号: 10205566
• 负责人: Serena-Kaye Kinley-Cooper Sims
• 金额: $ 7.48万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-07-31 至 2024-02-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10205566
• 关键词: Adult; Age; American; Animal Experimentation; Animals; Award; Behavioral; Binding; Biological Assay; Brain; Brain Injuries; Cell Death; Cell Survival; Consensus; Contralateral; Coupled; Data; Development; Dopamine; Educational process of instructing; Effectiveness; Electric Stimulation; Equilibrium; Exercise; Felis catus; Foundations; Frequencies; Glutamates; Goals; Human; Infarction; Injury; Institution; Intervention; Ischemic Penumbra; Lead; Lesion; Limb structure; Link; Love; Mentors; Modeling; Molecular; Motor; Motor Cortex; Nerve Growth Factors; Neuronal Plasticity; Neurons; Neurotransmitters; Neurotrophic Tyrosine Kinase Receptor Type 2; Paresis; Pathway interactions; Performance; Pharmacology; Phase; Pilot Projects; Play; Positioning Attribute; Postdoctoral Fellow; Rattus; Recovery; Recovery of Function; Rehabilitation therapy; Research; Research Project Grants; Research Training; Role; Running; Side; Signal Pathway; Signal Transduction; Stroke; Structure; Students; Techniques; Therapeutic; Training; Transcranial magnetic stimulation; United States; aged; behavioral study; controlled cortical impact; cost; experience; improved; juvenile animal; male; mature animal; motor deficit; motor function improvement; motor impairment; motor recovery; motor rehabilitation; neurogenesis; post stroke; post-doctoral training; relating to nervous system; repaired; response; skills; stroke recovery; stroke rehabilitation; stroke survivor; theories; tool; translational scientist; undergraduate student; young adult

Effects of Cortical Stimulation on Motor Recovery Cortical stimulation (CS) techniques, such as epidural cortical stimulation (ECS) and repeated transcranial magnetic stimulation (rTMS), are emerging as potential therapeutic tools to enhance the efficacy of post-stroke rehabilitation. Excitatory electrical cortical stimulation (eCS) or repeated Transcranial Magnetic Stimulation (rTMS) over the infarcted motor cortex, or disruptive low-frequency rTMS over the contralateral non-infarcted motor cortex, can lead to motor improvements of the paretic limb. Current theories suggest that cortical stimulation following ischemic damage “re- balances” interhemispheric activity between the non-infarcted and infarcted hemispheres interconnected via reciprocal excitatory circuits. In humans, facilitatory stimulation (high- frequency) ECS or rTMS over the infarcted motor cortex or disruptive stimulation (low- frequency) rTMS has been shown to improve performance of the paretic side; however, several studies also fail to support these findings. In rats, we and others have found that high-frequency (50Hz – 100Hz) ECS over the peri-lesion motor cortex following a focal, moderate stroke concurrent with motor rehabilitative training (RT), robustly improves functional motor recovery. Peri-infarct ECS+RT also results in functional and structural neural plasticity in the remaining motor cortex compared to RT alone. However, following severe strokes or controlled cortical impacts, a model of moderate to severe TBI, ipsi- injury high-frequency ECS+RT sub-optimally improves recovery compared to RT alone. We hypothesize that following moderate to severe damage to the motor cortex, low- frequency stimulation over the non-infarcted motor cortex concurrent with RT will be more effective at improving impaired motor function compared to high-frequency ipsi- injury ECS+RT or RT alone. BDNF binding to TrkB is necessary and sufficient to improve motor function and drive neural plasticity after stroke. CS+Rt also provides motor recovery through CS's ability to increase BDNF/TrkB signaling. We also hypothesize that this facilitation may be sensitive to endogenous BDNF/TrkB activity altered by age, and that pharmacological enhancement of TrkB signaling will maximize CS effects in aged animals.These studies will lay the foundation to better understand the lack of consensus across studies and to begin investigating the mechanisms underlying CS effects in stroke recovery.

皮层刺激对运动恢复的影响 皮质刺激（CS）技术，如硬膜外皮质刺激（ECS） 和重复经颅磁刺激（rTMS），正在成为潜在的 治疗工具，以提高中风后康复的疗效。兴奋性 皮层电刺激（eCS）或重复经颅磁刺激 （rTMS）在梗塞的运动皮层，或破坏性的低频rTMS在 对侧非梗死运动皮层，可导致麻痹患者的运动改善 四肢目前的理论表明，缺血性损伤后的皮层刺激“重新”， 平衡非梗死半球和梗死半球之间的半球间活动 通过相互的兴奋回路相互连接。在人类中，易化刺激（高- 频率）ECS或rTMS或破坏性刺激（低- 频率）rTMS已经显示出改善了麻痹侧的表现;然而， 一些研究也未能支持这些结论。在老鼠身上，我们和其他人发现， 在局灶性， 中度中风同时进行运动康复训练（RT）， 运动功能恢复梗死周围ECS+RT还导致功能和结构性 与单独RT相比，其余运动皮层的神经可塑性。但是随着 严重中风或控制皮质撞击，中度至重度TBI模型，ipsi- 与单独RT相比，损伤高频ECS+RT次优地改善了恢复。 我们假设在运动皮层中度到重度损伤后，低- 与RT同时进行的非梗死运动皮层的频率刺激将是 与高频ipsi相比，更有效地改善受损的运动功能- 损伤ECS+RT或单独RT。BDNF与TrkB的结合是必要的，也是足够的， 改善中风后运动功能和驱动神经可塑性。CS+Rt还提供 通过CS增加BDNF/TrkB信号传导的能力来恢复运动。我们也 假设这种促进作用可能对内源性BDNF/TrkB活性敏感 随着年龄的增长，TrkB信号的药理学增强将最大化 这些研究将为更好地了解CS在老年动物中的作用奠定基础。 缺乏共识的研究和开始调查的机制， CS在中风恢复中的作用。