Basic fibroblast growth factor (bFGF) enhances functional recovery following severe spinal cord injury to the rat

We have recently demonstrated that following a moderate contusion spinal co rd injury (SCI) to rats, subsequent administration of basic fibroblast grow th factor (bFGF) significantly enhances functional recovery and tissue spar ing. To further characterize the effects of bFGF, we evaluated its efficacy after a more severe contusion injury at T-10 using the NYU impactor. Immed iately after SCI, osmotic minipumps were implanted into the lateral ventric le and lumbar thecal sec to deliver bFGF at 3 or 6 mu g per day versus cont rol vehicle for 1 week. Animals were behaviorally tested for 6 weeks before histological assessment of tissue sparing through the injured segment and glial reactivity distal to the lesion. Compared to moderate SCI, all rats h ad more prolonged and sustained functional deficits 6 weeks after severe co ntusion. Subjects treated with bFGF had pronounced recovery of hindlimb mov ements from 2 to 6 weeks compared to controls, manifested in significantly higher behavioral scores. Only marginal tissue sparing was seen rostral to the injury in bFGF-treated spinal cords versus controls. Optical density me asurements of astrocyte and microglial cell immunoreactivity in bFGF-treate d spinal cords showed that after 6 weeks they approximated controls, althou gh astrocyte immunoreactivity remained higher in controls rostrally. In sum mary, intrathecal infusion of bFGF following severe SCI significantly resto res gross hindlimb motor function that is not correlated with significant t issue sparing. In light of previous evidence that pharmacological intervent ion with bFGF after moderate SCI enhances tissue preservation, the current findings indicate that yet undefined mechanisms contribute to the enhanced functional recovery following bFGF treatment. (C) 2000 Academic Press.