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.
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