Spinal Cord Injury, Plasticity and Transplant Mediated Repair

描述（由申请人提供）： 我们的长期目标是开发可用于临床的急性和慢性脊髓损伤（SCI）治疗方法。治疗干预，如移植和运动（EX），导致脊髓重组，如解剖，生理和行为分析所示。我们的项目将解决移植（TP）介导的功能恢复的影响和恢复对本地和/或远程站点的行动的依赖。项目1将重点关注成年大鼠SCI后移植神经限制性前体细胞（神经元和神经胶质细胞）的益处。将探讨干细胞IP促进神经保护、长距离轴突生长、跨病变传递信息和支持功能恢复的基本机制。项目2将使用脊髓损伤的猫来测试产生神经营养因子的IP获得的行为恢复是否是轴突再生或局部营养效应的结果。实验将测试损伤后移植延迟时的功能恢复，并将确定训练或移植后对腰部运动回路（即CPG）重组的感觉和运动影响。项目3将使用脊髓损伤大鼠来研究IP和EX介导的脊髓回路重组机制。活动依赖的可塑性是否创造了一个更有利于轴突再生的环境，以及神经肌肉接头的可塑性是否与改善的功能能力有关，这些都将被研究。行政核心将组织方案规划补助金参与者的每周会议，编写进度报告，并维持整个方案规划补助金预算。行为和生物力学核心将对SCI动物进行既定和新颖的行为评估，以确定损伤和治疗的影响，并提供对恢复机制的见解。细胞和分子生物学核心将为移植提供干细胞和修饰的成纤维细胞，并协助PCR和蛋白质测定。组织学核心将制备用于道追踪和免疫细胞化学反应的组织切片，并对TP介导的轴突再生和发芽进行图像分析。外科核心将协助准备SCI动物和移植程序。我们的策略是采用多种损伤模型和治疗组合来促进修复并了解功能恢复的机制。该计划与未来SCI治疗计划的设计和实施直接相关。

DESCRIPTION (provided by applicant): Our long-term goal is to develop treatments for acute and chronic spinal cord injury (SCI) that can be translated into the clinic. Therapeutic interventions, such as transplantation and exercise (EX), lead to reorganization of the spinal cord, as shown by anatomical, physiological and behavioral assays. Our Projects will address transplant (TP)-mediated effects on recovery of function and the reliance of recovery on actions at local and/or distant sites. Project 1 will focus on the benefits offered by transplantation of neural restricted precursor cells (neuronal and glial) after adult rat SCI. Basic mechanisms by which stem cell IPs promote neuroprotection, long distance axonal growth, relay information across a lesion and support recovery of function will be explored. Project 2 will use spinalized cats to test whether behavioral recovery attained with neurotrophin-producing IPs results from axonal regeneration or local trophic effects. Experiments will test for recovery of function when transplantation is delayed after injury and will define sensory and motor influences on reorganization of lumbar locomotor circuits (i.e. CPG) after training or transplantation. Project 3 will use spinalized rats to address mechanisms of IP- and EX-mediated reorganization of spinal cord circuitry. Whether activity-dependent plasticity creates an environment more conducive to axonal regeneration and if plasticity of neuromuscular junctions relates to improved functional capabilities will be examined. The Administration Core will organize weekly meetings of PPG participants, prepare progress reports and maintain the entire PPG budget. The Behavior and Biomechanics Core will conduct established and novel behavioral assessments of SCI animals to specify the effects of lesions and treatments and to provide insights into recovery mechanisms. The Cell and Molecular Biology Core will provide stem cells and modified fibroblasts for transplantation and assist with PCR and protein assays. The Histology Core will prepare tissue sections for tract tracing and immunocytochemical reactions and perform image analysis of TP-mediated axonal regeneration and sprouting. The Surgery Core will assist with preparation of SCI animals and transplantation procedures. Our strategy is to employ multiple injury models and combinations of treatments to promote repair and to understand mechanisms of functional recovery. This program has direct relevance to the design and implementation of future treatment programs for SCI.