Cerebellar stimulation for motor recovery from stroke

描述(由申请人提供)： 促进中风后患者运动恢复的选择极其有限，目前对长期治疗的护理标准包括转诊至物理治疗。尽管中风是美国的第三大死因，但每年70万人中的大多数人都会幸免于难。在这些幸存者中，50%将经历某种程度的单侧瘫痪，这是导致中风患者残疾和丧失独立性的主要原因{协会，2003#50}。除了对生活质量的影响外，重大的经济影响直接来自患者护理和康复成本以及患者劳动力生产力的损失，间接来自劳动力转移到照顾患者。该项目的目标是评估一种新的方法，通过增加皮层的兴奋性，从而通过慢性电刺激慢性缺血性中风啮齿动物模型的小脑深部结构来增强可塑性，从而促进中风后的运动恢复。这一设想的中心假设是，人工激活DTC通路将导致大脑皮层运动区兴奋性增强，从而促进神经元的可塑性和运动功能的恢复。为此，将在小脑外侧核植入微电极，以在已建立的中风啮齿动物模型中提供慢性电刺激。第一个目标是在啮齿动物模型中确定电刺激DTC通路的参数，以优化皮质运动的兴奋性，以运动诱发电位为指标。这些结果将被用来改进用于特定目标2的参数，这是一项涉及在已建立的缺血性中风啮齿动物模型中对DTC通路进行慢性电刺激的对照研究，以评估其对运动恢复的影响。这项应用的第三个目的是通过检查与治疗相关的改善对前肢远端还是近端的改善更大，来处理治疗益处的分配，这一信息将对患者选择有一定的好处。在这个模型中应用的治疗类似于脑深部刺激的治疗应用，已经被证明在治疗帕金森氏病和特发性震颤方面是安全有效的。因此，在硬件和技术已经很好的情况下，从一项最终提出的研究中获得的有希望的结果可能会直接导致对中风患者的试验。

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.