Paranodal demyelination in chronic spinal cord compression. (360G-Wellcome-085360_Z_08_Z)

Chronic spinal cord compression (due to tumours, disc protrusions etc) is a common clinical problem but both the mechanisms of progressive loss of function and the effects of surgical decompression on cellular and sub-cellular physiology are incompletely understood. Both these issues are of high clinical importance, given the high incidence of cord compression and large numbers of decompressive surgeries conducted worldwide every year in human an animal patients. The host laboratory has deve loped a recently described model of chronic cord compression in which an expandable polymer sheet is placed over the cervical spinal cord. Histological examination has demonstrated that there are many deficits in myelin structure associated with compression and, furthermore, that decompression through atraumatic removal of the polymer sheet is associated with evidence of free-radical mediated cellular injury. This project will expand and quantify these preliminary observations by examining two a spects of the relationships between hypoxia, myelin disruption axonal dysfunction and axonal loss: firstly, that during chronic compression; and, secondly, that occurring immediately after decompression. These investigations will focus on the production of free radicals in compressed and decompressed tissue, disruption of nodal structure and its correlation with axonal destruction.