RECOVERY OF FUNCTION AFTER SPINAL CORD INJURY

脊髓损伤后的功能恢复

• 批准号: 2266270
• 负责人: BARBARA S BREGMAN
• 金额: $ 24.37万
• 依托单位: GEORGETOWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-04-01 至 1997-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2266270
• 关键词: animal tissue; axon; brain stem; chordate locomotion; disease /disorder model; dorsal root; embryo /fetus cell /tissue; functional ability; immunocytochemistry; laboratory rat; mature animal; motor cortex; nervous system regeneration; nervous system transplantation; neural plasticity; neuroanatomy; neurons; neurotrophic factors; newborn animals; nonhuman therapy evaluation; photolysis; pyramidal tracts; spinal cord injury; transmission electron microscopy

The consequences of spinal cord injury and subsequent recovery of function in newborn and adult rats are not uniform. The observation that the locomotor patterns and motor strategies which recover after spinal cord injury differ between newborn and adult operates suggests that the mechanisms underlying this recovery also must differ. The long range goal of this research program is to define the mechanisms underlying recovery of function following spinal cord injury and to identify methods to enhance that recovery. During the previous period of support we have demonstrated that transplants of fetal spinal cord tissue (homotypic transplants) mediate recovery of function after spinal cord injury in newborn and adult rats. This recovery of function is dependent upon anatomical integration of the transplant with the host CNS and the formation of connections between host and transplant. We have also demonstrated, however, that non-target (heterotypic) transplants are also capable of modifying behavioral recovery. The experiments in the current proposal will test the hypothesis that transplants of fetal spinal cord tissue mediate recovery of function both by specific mechanisms (i.e. permitting the regeneration of particular descending and segmental pathways) and by non-specific mechanisms (such as trophic effects). The studies proposed will determine the contribution of anatomical reorganization to recovery of function after spinal cord lesions in newborn and adult rats. We hypothesize that segmental, intersegmental and suprasegmental pathways make unique contributions to anatomical plasticity and recovery of function after spinal cord lesions and transplants and that their relative contribution differs following lesions in the adult versus lesion in the neonate. Studies are also proposed to test the hypothesis that the administration of exogenous trophic support will increase both the extent of regeneration and the degree of recovery of function after spinal cord injury and transplantation in neonatal and adult operates. We will continue to use our model system of spinal cord injury and transplantation in newborn and adult rats. We will examine the response to injury of 4 representative pathways, which differ in their relative stages of their development at birth and determine their contribution to recovery of function. The studies proposed use sensitive qualitative and quantitative behavioral analysis of specific tests of reflex and locomotor function, and qualitative and quantitative neuroanatomical tracing techniques to determine the mechanisms which underlie recovery of function after spinal cord injury in the developing and mature CNS and to identify ways to enhance that recovery.

脊髓损伤的后果和随后的恢复 新生儿和成年大鼠的功能并不均匀。 观察到 脊柱后恢复的运动模式和运动策略 新生儿和成人手术之间的绳索损伤表明 此恢复的基础机制也必须有所不同。 远距离 该研究计划的目标是定义基本机制 脊髓损伤后功能的恢复并确定方法 为了增强这种恢复。 在上一个支持期间，我们有 证明了胎儿脊髓组织的移植（同型 移植）介导脊髓损伤后功能的恢复 新生儿和成年大鼠。 功能的恢复取决于 移植与宿主中枢神经系统的解剖整合和 主机和移植之间的连接形成。 我们也有 然而，证明非目标（异型）移植也是 能够修改行为恢复。 电流中的实验 提案将检验胎儿脊髓移植的假设 组织通过特定机制介导功能的恢复（即 允许对特定下降和分段的再生 途径）和非特异性机制（例如营养效应）。 这 提出的研究将确定解剖学的贡献 重组脊髓病变后功能的恢复 新生儿和成年大鼠。 我们假设该分段，段 和上段途径为解剖学做出了独特的贡献 脊髓病变后的可塑性和功能恢复 移植，其相对贡献在遵循 新生儿的成人与病变的病变。 研究也是 提出了测试外源性的假设 营养支持将增加再生的程度和 脊髓损伤后功能的恢复程度和 新生儿和成人的移植。 我们将继续使用 我们在新生儿中的脊髓损伤和移植的模型系统 成年大鼠。 我们将研究对4位代表的伤害的反应 途径在其发展的相对阶段有所不同 分娩并确定其对功能恢复的贡献。 这 研究建议使用敏感的定性和定量行为 分析反射和运动功能的特定测试，以及 定性和定量的神经解剖学跟踪技术 确定脊柱后功能恢复的机制 发育中心和成熟的中枢神经系统中的绳索损伤，并确定方法 增强恢复。