Rehabilitation Mechanisms of Hand Motor Recovery After Sensorimotor Cortex Injury

中风通常累及大脑皮层，是影响功能性残疾的主要原因 在美国，每年有近80万人。集体对个人、社会的负面影响 这种混乱带来的经济影响令人震惊。常见的临床后果之一 最常见的中风形式之一，即大脑中动脉梗塞，是严重的 由于初级运动皮质受损而导致的上肢运动功能障碍 (M1)和邻近的顶叶躯体感觉皮质(S1)。尽管看起来似乎有 成人大脑相当大的功能可塑性，运动恢复的机制 脑损伤后的M1和S1仍然知之甚少。我们的主要目标是测试 假设M1后手和手臂运动功能恢复的中心机制 而S1损伤是通过从备用运动皮质到 脑干和脊髓因强迫使用理疗所致。我们期待着 良好的运动恢复和增强的轴突重组将伴随着 上调神经营养分子因子。我们还计划研究习得的不使用如何影响 这些相同的分子和连接反应的目标是精确定位细胞 可作为多模式治疗干预目标的机制 对电流无反应的M1和S1皮质损伤严重受损的患者 治疗。我们将研究这些来自备用区域的分子和轴突重塑反应 受伤和未受伤的大脑半球，因为这些大脑区域代表着高度可及的 卒中患者非侵入性和侵入性治疗干预策略的目标。 备用皮质脊髓和皮质球投射的神经可塑性反应将是相关的 神经营养因子信号传递和手臂和手的运动恢复使用多个， 最先进的解剖学、分子和行为方法学。这个项目将导致一个 更好地了解备用轴突投射系统和 双侧大脑半球神经营养因子基因调控谱与手臂康复的关系 以及在强制使用治疗和高级习得不使用后的手部运动。这 信息还将有助于识别可能作为重要的内部 应用创造性、非侵入性和侵入性疗法以增强运动能力的资源 常见的外侧皮质损伤后的恢复。

Stroke often involves the cerebral cortex and is a leading cause of functional disability affecting nearly 800,000 people per year in the United States. The collective negative personal, social and economic impacts of this disorder are staggering. One of the common clinical consequences of the most frequent form of stroke, namely middle cerebral artery infarction, is severe impairment of upper extremity motor function because of damage to the primary motor cortex (M1) and the adjacent parietal somatosensory cortex (S1). Although there appears to be considerable functional plasticity in the adult brain, the mechanisms underlying motor recovery following brain injury to both M1 and S1 remain poorly understood. Our major goal is to test the hypothesis that a central mechanism of functional recovery of hand and arm movement after M1 and S1 injury occurs through reorganization of axon connections from spared motor cortex to the brainstem and spinal cord as a result of forced use physical therapy. We expect that favorable motor recovery and enhanced axonal reorganization will be accompanied by upregulated neurotrophic molecular factors. We also plan to study how learned non-use affects these same molecular and connectional responses with the goal of pinpointing cellular mechanisms that can serve as targets for multimodal therapeutic interventions in moderate to severely impaired patients with cortical injury to M1 and S1 who do not respond to current therapies. We will study these molecular and axon remodeling responses from spared regions of the injured and uninjured hemisphere, because these brain regions represent highly accessible targets for non-invasive and invasive therapeutic intervention strategies in stroke patients. Neuroplastic responses of spared corticospinal and corticobulbar projections will be correlated with neurotrophic factor signaling and recovery of arm and hand movements using multiple, state-of-the art anatomical, molecular and behavioral methodologies. This project will lead to a greater understanding of the contribution of spared axonal projection systems and corresponding neurotrophin gene regulation profiles in both hemispheres to recovery of arm and hand movement following forced-use therapy and advanced learned non-use. This information will also assist in identifying cortical targets that may serve as important internal resources for the application of creative, non-invasive and invasive therapies to enhance motor recovery after common lateral cortical injury.