SENSORY FUNCTION RECOVERY FOLLOWING ANTEROLATERAL CORDOTOMY

前外侧皮质切开术后的感觉功能恢复

• 批准号: 6112119
• 负责人: Elizabeth Bullitt
• 金额: $ 11.26万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 1998
• 资助国家: 美国
• 起止时间: 1998-06-01 至 2001-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6112119
• 关键词: NMDA receptors; afferent nerve; disease /disorder model; dorsal root; electron microscopy; electrostimulus; gene expression; immunocytochemistry; laboratory rat; nervous system regeneration; neural plasticity; neurotrophic factors; pain; pyramidal tracts; regulatory gene; reticulospinal tract; sensory mechanism; sensory receptors; spinal cord injury; spinal cord mapping; spinal cord surgery; spinal ganglion; stimulus /response; thalamocortical tract; thrombin

The long-term goal of this project is to determine the mechanisms underlying the gradual return of sensory function that sometimes occurs in human beings and other mammals following spinal cord injury. Anterolateral cordotomy, an operation used to treat pain in human cancer patients, is used as a model of controlled spinal injury in behaviorally trained rodents. In the rat, as in the human and non-human primate, approximately 50% of subjects develop delayed sensory recovery after an initially successful operation. This variability in recuperative potential provides the opportunity to differentiate between animals that recover and those that do not, with the purpose of identifying the specific factors that promote recovery from neural injury. This proposal examines the hypothesis that specific immediate early genes, or specific levels of growth promoters or growth inhibitors, may be related to delayed recovery following neural injury. The focus of these experiments is upon the spinal cord. Both immunohistochemical and molecular biological technique will be used to detect levels of gene expression and protein production. The specific questions to be asked are; 1) Does the intraspinal expression of the immediate early genes c-fos and c-jun following anterolateral cordotomy represent a specific or a non- specific injury response? Can such gene expression be correlated with the development of sensory recovery? In particular, a) what is the time course of gene expression? b) is the pattern of gene expression dependent upon lesion configuration? c) can levels of gene expression be correlated with functional recovery? 2) Do animals that recover sensory function after cordotomy show higher intraspinal levels of the neurite growth promoter PN-1, and lower intraspinal levels of the endogenously produced, neurite growth inhibitor thrombin, than animals that fail to recover? If neural recovery following spinal injury can be correlated with the expression of particular genes or with the production of specific proteins, than a potentially powerful avenue for patient treatment could become available.

这个项目的长期目标是确定机制 在感觉功能逐渐恢复的基础上，有时发生在 人类和其他哺乳动物脊髓损伤后。前外侧 心脏切断术是一种用于治疗癌症患者疼痛的手术， 在行为训练中用作受控脊髓损伤的模型 啮齿动物。在老鼠中，如在人类和非人类灵长类动物中，大约 50%的受试者在最初的感觉恢复后出现延迟 手术成功。这种恢复力的可变性提供了 有机会区分康复的动物和 不是这样的，目的是为了找出 促进神经损伤的恢复。 这一建议检验了特定的即刻早期基因， 或特定水平的生长促进剂或生长抑制剂，可能与 神经损伤后恢复延迟。这些问题的焦点 实验发生在脊髓上。免疫组织化学和 分子生物学技术将被用于检测基因水平 表达和蛋白质生产。 要问的具体问题是； 1)即刻早期基因c-fos和c-fos在脊髓内的表达 脊髓前外侧切开术后的c-jun代表一种特殊的或非 具体的伤害反应？这样的基因表达是否与 感觉恢复的发展？具体而言，a)时间进程是什么 关于基因表达的？B)基因表达模式依赖于 损伤结构？C)基因表达水平是否与 功能恢复？ 2)脊髓切断术后感觉功能恢复的动物表现得更好吗 神经突起生长启动子PN-1及更低水平的脊髓内表达 脊髓内内源性神经突起生长抑制物的水平 凝血酶，而不是无法恢复的动物？ 如果脊髓损伤后的神经恢复可以与 特定基因的表达或特定蛋白质的产生， 可能成为治疗病人的一个潜在的有效途径 可用。