Rehabilitation Mechanisms of Hand Motor Recovery After Sensorimotor Cortex Injury

感觉运动皮层损伤后手部运动恢复的康复机制

• 批准号: 9276823
• 负责人: ROBERT J MORECRAFT
• 金额: $ 39.41万
• 依托单位: UNIVERSITY OF SOUTH DAKOTA
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-07-01 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9276823
• 关键词: Adult; Affect; Anatomy; Animals; Area; Axon; Behavioral; Brain; Brain Injuries; Brain Stem; Brain region; Cell Nucleus; Cerebral cortex; Clinical; Coupled; Databases; Development; Disease; Down-Regulation; Event; Excision; Fingers; Gene Expression Regulation; Goals; Hand; Hand functions; Human; Impairment; Individual; Injury; Intervention; Label; Lateral; Lesion; Lifting; Limb structure; Long-Term Effects; Macaca mulatta; Methodology; Middle Cerebral Artery Infarction; Modeling; Molecular; Motion; Motor; Motor Cortex; Motor Skills; Movement; Neuronal Plasticity; Outcome; Parietal; Pathway interactions; Patients; Pharmacological Treatment; Pharmacology; Physical therapy; Play; Primates; Process; Recovery; Recovery of Function; Rehabilitation therapy; Research Project Grants; Resources; Reticular Formation; Role; Side; Signal Transduction; Social Impacts; Somatosensory Cortex; Spinal; Spinal Cord; Stroke; System; Testing; Therapeutic; Therapeutic Intervention; United States; Upper Extremity; Work; arm; arm movement; constraint induced movement therapy; density; economic impact; functional disability; functional plasticity; grasp; gray matter; hand dysfunction; improved; injured; interest; motor control; motor recovery; motor rehabilitation; multi-component intervention; multimodality; neural circuit; neurotrophic factor; neurotropin; response; skills

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.

中风通常累及大脑皮层，是影响脑功能障碍的主要原因。 在美国每年有近80万人死亡。集体消极的个人，社会 和经济影响是惊人的。一个常见的临床后果 最常见的中风形式，即大脑中动脉梗塞， 由于初级运动皮层受损导致上肢运动功能受损 (M1)和相邻的顶叶体感皮层（S1）。虽然看起来 成人大脑中相当大的功能可塑性，运动恢复的机制 脑损伤后对M1和S1的影响仍然知之甚少。我们的主要目标是测试 M_1术后手和臂运动功能恢复中枢机制假说 而S1损伤是通过从备用运动皮层到 脑干和脊髓因为强迫使用物理治疗。我们预计 有利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性不使用如何影响 这些相同的分子和连接反应， 可以作为多模式治疗干预的目标的机制， 对电流无反应的M1和S1皮质损伤的严重受损患者 治疗我们将研究这些分子和轴突重塑反应，从备用地区的 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性， 为中风患者的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延髓投射的神经可塑性反应将是相关的 随着神经营养因子信号传导和手臂和手部运动的恢复， 最先进的解剖学分子和行为学方法该项目将导致一个 更好地理解备用轴突投射系统的贡献， 两个半球中相应的神经营养因子基因调控谱对手臂恢复 和强迫使用治疗后的手部运动和高级学习不使用。这 这些信息还将有助于识别可能作为重要的内部靶点的皮质靶点， 资源的应用创造性，非侵入性和侵入性疗法，以提高运动 常见外侧皮质损伤后恢复。