TRAUMATIC BRAIN INJURY IN RATS RESULTS IN INCREASED EXPRESSION OF GAP-43 THAT CORRELATES WITH BEHAVIORAL RECOVERY

Traumatic brain injury is associated with behavioral deficits, often i n the absence of histopathological or ultrastructural changes. To dete rmine whether membrane remodeling occurs, immunocytochemical technique s were used and the density and distribution of GAP-43 were measured. GAP-43 is a membrane-bound protein, which, when phosphorylated, is tho ught to regulate metabolic pathways involved in membrane remodeling an d neurite growth. Moderate central fluid percussion injury (FPI, 1.9-2 .2 atm.) was performed on anesthetized, spontaneously hypertensive Wis tar rats (SHR). Behavioral reflex recovery was consistent with moderat e levels of brain injury. One, 3, 5, 7 and 9 days after injury, both s ham control (n = 4) and FPI (n = 4) animals were sacrificed, the brain s were removed, cryosectioned and processed. Density measurements were taken from histological sections taken at interaural 6.20 mm and breg ma -2.80 mm and were found to be statistically greater (P < 0.05) than background grey matter readings in the agranular cortices, the fronta l, hindlimb, parietal 1 and 2 cortices, and the hippocampus and dentat e gyrus, excluding the pyramidal and granular cell layers. Density mea surements taken in forelimb and hindlimb cortical regions correlate wi th forelimb and hindlimb recovery in foot-fault and beam balance tests (P < 0.05). We interpret these data to indicate neuronal membrane rem odeling as a result of the disruption of neuronal membranes due to the impact and shearing forces associated with the FPI. The disruption an d remodeling of neuronal membranes are in areas that are consistent wi th the loss and recovery of locomotor and spatial behavior as a result of FPI. (C) 1998 Published by Elsevier Science Ireland Ltd. All right s reserved.