Cerebellar stimulation for motor recovery from stroke

描述（由申请人提供）： 提高中风后患者运动恢复的选择非常有限，目前的长期治疗标准包括转诊到物理治疗。虽然中风是美国的第三大死因，但每年70万人中的大多数人都能幸存下来。在这些幸存者中，50%将经历某种程度的单侧瘫痪，这是中风患者残疾和丧失独立性的主要原因{Association，2003 #50}。除了对生活质量的影响外，患者护理和康复成本以及患者劳动力生产力的损失直接产生了重大的经济影响，间接影响来自劳动力的转移。拟议项目的目标是评估一种新的方法，以提高运动恢复中风后，通过增加皮质兴奋性，因此，通过慢性电刺激小脑深部结构的慢性，缺血性中风的啮齿动物模型的可塑性。该建议的中心假设是，人工激活净兴奋性dentatothalamocortical（DTC）通路将导致大脑皮层运动区的兴奋性增加，促进神经元的可塑性和运动功能的恢复。为此，将微电极植入小脑外侧核，以便在已建立的啮齿动物中风模型中输送慢性电刺激。第一个目标是确定啮齿动物模型中DTC通路的电刺激参数，其优化皮质运动兴奋性，如使用运动诱发电位所索引的。这些结果将用于改进特定目标2中使用的参数，该目标2是一项对照研究，涉及在已建立的缺血性卒中啮齿动物模型中对DTC通路进行慢性电刺激，以评价对运动恢复的影响。本申请的第三个目的是通过检查治疗相关的改善对于远侧或近侧前肢是否更大来处理治疗益处的分布，该信息将在患者选择中具有一些益处。在该模型中应用的治疗类似于深部脑刺激的治疗应用，其已经被证明在帕金森病和原发性震颤的治疗中是安全有效的。因此，从一项研究中获得的有希望的结果，如最终提出的研究，可能会直接导致在中风患者中进行试验，因为硬件和技术已经很好地建立起来。

DESCRIPTION (provided by applicant): Options for enhancing patient motor recovery following stroke are extremely limited, with current standard of care for long-term treatment comprised of referral to physical therapy. Although stroke is the third leading cause of death in the United States, the majority of the 700,000 individuals afflicted each year will survive the event. Of those survivors, 50% will experience some degree of one-sided paralysis, the leading cause of disability and loss of independence among stroke patients {Association, 2003 #50}. In addition to quality of life implications, substantial economic impact arises directly from patient care and rehabilitation costs as well as loss of patient workforce productivity, and indirectly from the displacement of labor to care for the patient. The goal of the proposed project is to evaluate a novel approach to enhancing motor recovery following stroke by increasing cortical excitability and, consequently, plasticity through chronic electrical stimulation of the deep cerebellar structures in a rodent model of chronic, ischemic stroke. The central hypothesis of this proposal is that artificial activation of the net excitatory dentatothalamocortical (DTC) pathway will result in increased excitability of motor regions of cerebral cortex, facilitating neuronal plasticity and recovery of motor function. To this end, microelectrodes will be implanted in the lateral cerebellar nucleus for the purpose of delivering chronic electrical stimulation in an established rodent model of stroke. The first aim will be to determine the parameters of electrical stimulation of the DTC pathway in the rodent model that optimize cortical motor excitability, as indexed using motor evoked potentials. These results will be used to refine the parameters used in specific aim two, a controlled study involving chronic electrical stimulation of the DTC pathway in an established rodent model of ischemic stroke in order to evaluate the effect on motor recovery. The third aim of this application deals with the distribution of therapeutic benefit by examining whether treatment-related improvement is greater for the distal or proximal forelimb, information that will be of some benefit in patient selection. The treatment applied in this model is analogous to the therapeutic application of deep brain stimulation, which already has been demonstrated to be safe and effective in the treatment of Parkinson's disease and essential tremor. Thus, promising results from a study such as the one proposed ultimately could lead directly to trials in human patients with stroke as the hardware and techniques are already well established.