Exercise, Intraspinal Transplants and Spinal Cord Plasticity

运动、椎管内移植和脊髓可塑性

• 批准号: 8534982
• 负责人: John D. Houle
• 金额: $ 25.51万
• 依托单位: DREXEL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/8534982
• 关键词: Acute; Address; Adult; Affect; Afferent Neurons; Animal Model; Animals; Area; Axon; Back; Behavior; Behavioral; Brain-Derived Neurotrophic Factor; Chest; Chondroitinases; Chronic; Control Animal; Cues; Digestion; Distal; Electrophysiology (science); Exercise; Felis catus; Fibroblasts; Future; Growth; H-Reflex; Hindlimb; Hyaluronidase; Individual; Injury; Instruction; Label; Length; Lesion; Lumbar spinal cord structure; Mediating; Mental Depression; Methods; MicroRNAs; Modeling; Motor; Motor Neurons; Muscle; NTF3 gene; Natural regeneration; Neurons; Operative Surgical Procedures; Patients; Perception; Peripheral Nerves; Preparation; Procedures; Process; Proteins; Proteoglycan; Rattus; Recovery; Recovery of Function; Research Personnel; Sensory; Site; Source; Spinal; Spinal Cord; Spinal Cord Plasticity; Spinal cord injury; Staging; Step training; Synapses; Testing; Thoracic spinal cord structure; Time; Training; Translations; Transplantation; Up-Regulation; axon growth; axon regeneration; base; design; efficacy testing; functional improvement; improved; injured; kinematics; mRNA Expression; neurotrophic factor; pre-clinical; protein expression; receptor; regenerative; repaired; research study; response; restoration; spinal pathway; spinal reflex; success; treatment strategy; true blue

Experimental spinal cord injury (SCI) models have helped define levels of structural and functional plasticity within the spinal cord and affected muscles. Peripheral nerve grafts (PNGs) support the regeneration of acute and chronically injured neurons although growth beyond the graft, back into the spinal cord, is limited in terms of the number and length of axonal extension. Digestion of inhibitory proteoglycans with Chondroitinase is partially effective in increasing axonal outgrowth and there is evidence of functional synaptic connection between regenerated axons and spinal cord neurons. Exercise-induced increase of neurotrophic factors in thoracic and lumbar spinal cord is correlated with the restoration of motoneuron excitability (spinal reflexes) to near normal activity. Despite these successes there remain thousands of injured neurons that are not involved in reorganization and repair of the injured spinal cord. Our objectives are to address mechanistic questions related to the potential for exercise to provide trophic factor cues to potentially promote the regenerative response of injured neurons and/or to activate spinal networks to facilitate receptivity of regenerating axons. Aim 1 will address the hypothesis that exercise will promote regeneration of acute and/or chronically injured axons into a PNG, using an adult rat lower thoracic level transection injury, separate PNGs to support growth of descending vs. ascending axons and treadmill step training. Tract tracing methods will define the regenerative effort of motor and sensory neurons. Aim 2 will test whether exercise increases axonal outgrowth from a PNG and determine possible functional improve- ment related to regenerated axons by performing sensorimotor behavior, kinematic and electrophysiological analyses. In separate groups we will test whether activity-dependent plasticity is achieved with either/or an acute or delayed treatment approach. To advance the preclinical translation of our treatment strategy, results from SCI rats will be applied to a spinalized cat preparation to test whether exercise and transplantation promote regeneration-based functional recovery in a large animal model. Overall, these experiments will provide fundamental information about cellular and functional aspects of spinal cord reorganization in acute and chronic stages of SCI that will be instrumental in designing strategies for repair. RELEVANCE (See instructions): Here we will combine transplantation and exercise treatment strategies to determine if the regenerative effort of injured neurons can be enhanced in acute and chronically injured animals. This observation directiy impacts the overwhelming number of spinal cord injured patients because of the perception that most surgical interventions should be delayed until the individual is stable and opportunities for spontaneous recovery have subsided

实验脊髓损伤（SCI）模型有助于定义结构和功能可塑性水平