SENSORY FUNCTION RECOVERY FOLLOWING ANTEROLATERAL CORDOTOMY

本项目的长期目标是确定 这是感觉功能逐渐恢复的基础， 人类和其他哺乳动物的脊髓损伤。 前外侧 脊髓切断术，一种用于治疗人类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 在大鼠中，与人类和非人类灵长类动物一样，大约 50%的受试者在最初的感觉恢复后出现延迟 手术成功。 这种恢复潜力的可变性提供了 有机会区分恢复的动物和 目的是确定具体因素， 促进神经损伤的恢复。 这项提议检验了特定的立即早期基因， 或特定水平的生长促进剂或生长抑制剂，可能与 神经损伤后的延迟恢复 这些焦点 实验是在脊髓上进行的 免疫组织化学和 分子生物学技术将用于检测基因水平， 表达和蛋白质生产。 要问的具体问题是： 1)脊髓内即刻早期基因c-fos和 前外侧脊髓切断术后c-jun代表了一种特异性或非特异性的 具体伤害反应？ 这种基因表达是否与 感官恢复的发展 具体而言，a）时间进程是什么 基因表达？ B）是基因表达模式依赖于 病变结构？ c）基因表达水平是否与 功能恢复？ 2)脊髓切断术后恢复感觉功能的动物是否表现出更高的 脊髓内神经突生长促进剂PN-1的水平，以及更低的 脊髓内内源性神经突生长抑制剂水平 凝血酶，而不是动物未能恢复？ 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， 比一个潜在的强大的病人治疗途径可能成为 available.

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.