Cortical Stimulation to Enhance Recovery after Stroke

描述（由申请人提供）： 脑卒中后运动功能的恢复伴随着大脑皮层功能和结构的可塑性。在这个转化研究合作计划（U 54）中，一种新的治疗方法，旨在通过调节神经可塑性来增强运动恢复，将在大鼠（项目1和2）和非人灵长类动物（项目3）皮质缺血性梗死后恢复模型中进行测试。这种新的方法，皮质刺激（CS），利用低水平的电刺激在周围梗死皮层在康复训练过程中应用。在学术界和工业界的基础和临床研究人员的这种独特合作中，临床前模型将用于优化即将进行的临床试验的治疗方案。在项目1中，将优化电刺激方案（频率、振幅、时间模式、电极配置和持续时间），并检查癫痫发作敏感性。将根据诱发运动阈值和运动表现评估疗效。在项目2中，康复训练方案将通过将CS与不同的康复训练程序（约束诱导运动疗法、伸展训练、杂技训练）相结合来优化。将通过治疗和随访期间的运动表现评估训练程序的有效性。在项目3中，将测试在大鼠模型中确定的最佳参数对非人灵长类动物皮质缺血和恢复模型的可推广性。此外，将在灵长类动物中评估啮齿类动物模型中不太可行的给药参数。监督/领导核心将组织会议，促进科学交流，协助管理U 54核心和项目，并提供数据管理和生物统计支持。这三个项目将在四个研究中心进行，选择这些研究中心是因为研究人员在中风恢复领域拥有丰富的经验，而且他们组成了一个综合团队，推进了最初的临床前研究。临床前结果将通过临床前小组与临床试验医学总监和U 54指导委员会的定期会议转化为临床项目，以讨论a）临床前发现及其对临床项目的影响，以及B）可能影响临床前研究的临床项目发现。预计该计划将作为引入基于神经科学原理的脑修复新治疗方法的模型。

DESCRIPTION (provided by applicant): Motor recovery after stroke is accompanied by functional and structural plasticity in cerebral cortex. In this Cooperative Program in Translational Research (U54), a new therapeutic approach, intended to enhance motor recovery via modulation of neuroplasticity, will be tested in rat (Projects 1 and 2) and nonhuman primate (Project 3) models of recovery after cortical ischemic infarct. This new approach, Cortical Stimulation (CS), utilizes low-level electrical stimulation over peri-infarct cortex applied during rehabilitative training procedures. In this unique collaboration of basic and clinical researchers in academia and industry, preclinical models will be used to optimize treatment protocols for upcoming clinical trials funded by industry. In Project 1, the electrical stimulation protocol (frequency, amplitude, temporal pattern, electrode configuration and duration) will be optimized and seizure susceptibility will be examined. Efficacy will be assessed with regard to evoked movement thresholds and motor performance. In Project 2, the rehabilitative training protocol will be optimized by combining CS with different rehabilitative training procedures (constraint-induced movement therapy, reach training, acrobatic training). The efficacy of training procedures will be assessed by motor performance during treatment and follow-up. In Project 3, optimal parameters determined in rat models will be tested for generalizability to a nonhuman primate model of cortical ischemia and recovery. Also, treatment parameters that are less feasible in the rodent model will be assessed in primates. An Oversight/Leadership Core will organize meetings, promote scientific exchange, assist in management of U54 cores and projects and provide data management and biostatistical support. The three projects will be performed at four sites, chosen because the investigators have extensive experience in the field of stroke recovery, and because they form an integrated team that has advanced the initial preclinical studies. Preclinical results will be translated into the clinical program by regular meetings of the preclinical group with the medical director for clinical trials and U54 Steering Committee to discuss a) preclinical findings and their impact on the clinical program, and b) findings from the clinical program that may impact the preclinical studies. It is expected that this program will serve as a model for the introduction of new therapeutic approaches to brain repair that are based on underlying neuroscientific principles.