Effects of Cortical Stimulation on Motor Recovery

皮质刺激对运动恢复的影响

• 批准号: 10368104
• 负责人: Serena-Kaye Kinley-Cooper Sims
• 金额: $ 7.96万
• 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/10368104
• 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; 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; Students; Techniques; Therapeutic; Training; Transcranial magnetic stimulation; United States; aged; behavioral study; controlled cortical impact; cost; effectiveness analysis; effectiveness evaluation; experience; improved; juvenile animal; male; mature animal; motor deficit; motor function improvement; motor impairment; motor recovery; motor rehabilitation; neural repair; neurogenesis; post stroke; post-doctoral training; 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.

大脑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 提高中风后康复疗效的治疗工具。兴奋的 电皮质刺激(ECS)或重复经颅磁刺激 (RTMS)在梗塞的运动皮质上，或破坏性的低频rTMS在 对侧非梗死区运动皮质，可导致偏瘫患者的运动改善 四肢。目前的理论认为，脑缺血损伤后的皮质刺激“再... 平衡非梗死区和梗死区大脑半球间的活动 通过相互激励电路相互连接。在人类中，促进性刺激(高- 频率)ECS或rTMS在梗塞的运动皮质或干扰性刺激(低- 频率)rTMS已被证明可以改善偏瘫侧的表现；然而， 几项研究也未能支持这些发现。在老鼠身上，我们和其他人发现 病灶后在病变周围运动皮质上进行高频(50赫兹-100赫兹)ECS， 中度中风同时进行运动康复训练(RT)，病情明显好转 运动功能恢复。梗死区周围ECS+RT也可导致功能性和结构性 与单纯RT相比，其余运动皮质中的神经可塑性。然而，以下是 严重中风或受控皮质撞击，中度至重度脑外伤模型，ipsi- 与单纯RT相比，损伤高频ECS+RT次佳地改善了恢复。 我们假设在运动皮质受到中度到严重损伤后，低- 在RT的同时，对非梗死区运动皮质的频率刺激将 与高频ipsi相比，在改善受损的运动功能方面更有效 损伤ECS+RT或单纯RT。BDNF与TrkB的结合是必要且充分的 改善中风后的运动功能，促进神经可塑性。CS+RT还提供 运动恢复通过CS增加BDNF/TrkB信号的能力。我们也 假设这种促进作用可能对内源性BDNF/TrkB活性敏感 TrkB信号的药理增强将最大限度地 CS对老年动物的影响。这些研究将为进一步了解 在所有研究中缺乏共识，并开始调查潜在的机制 CS在中风康复中的作用。