NERVE GROWTH-FACTOR ADMINISTRATION ATTENUATES COGNITIVE BUT NOT NEUROBEHAVIORAL MOTOR DYSFUNCTION OR HIPPOCAMPAL CELL LOSS FOLLOWING FLUID-PERCUSSION BRAIN INJURY IN RATS

Lateral fluid-percussion brain injury in rats results in cognitive def icits, motor dysfunction, and selective hippocampal cell loss. Neurotr ophic factors have been shown to have potential therapeutic applicatio ns in neurodegenerative diseases, and nerve growth factor (NGF) has be en shown to be neuroprotective in models of excitotoxicity. This study evaluated the neuroprotective efficacy of intracerebral NGF infusion after traumatic brain injury. Male Sprague-Dawley rats received latera l fluid-percussion brain injury of moderate severity (2.1-2.3 atm). A miniosmotic pump was implanted 24 h after injury to infuse NGF (n = 34 ) or vehicle (n = 16) directly into the region of maximal cortical inj ury. Infusions of NGF continued until the animal was killed at 72 h, 1 week, or 2 weeks after injury. Animals were evaluated for cognitive d ysfunction (Morris Water Maze) and regional neuronal cell loss (Nissl staining) at each of the three time points. Animals surviving for 1 or 2 weeks were also evaluated for neurobehavioral motor function. Altho ugh an improvement in memory scores was not observed at 72 h after inj ury, animals receiving NGF infusions showed significantly improved mem ory scores when tested at 1 or 2 weeks after injury compared with inju red animals receiving vehicle infusions (p < 0.05). Motor scores and C A3 hippocampal cell loss were not significantly different in any group of NGF-treated animals when compared with controls. These data sugges t that NGF administration, in the acute, posttraumatic period followin g fluid-percussion brain injury, may have potential in improving postt raumatic cognitive deficits.