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 in the absence of histopathological or ultrastructural changes. To determine whether membrane remodeling occurs, immunocytochemical techniques were used and the density and distribution of GAP-43 were measured. GAP-43 is a membrane-bound protein, which, when phosphorylated, is thought to regulate metabolic pathways involved in membrane remodeling and neurite growth. Moderate central fluid percussion injury (FPI, 1.9-2.2 atm.) was performed on anesthetized, spontaneously hypertensive Wistar rats (SHR). Behavioral reflex recovery was consistent with moderate levels of brain injury. One, 3, 5, 7 and 9 days after injury, both sham control (n = 4) and FPI (n = 4) animals were sacrificed, the brains were removed, cryosectioned and processed. Density measurements were taken from histological sections taken at interaural 6.20 mm and bregma -2.80 mm and were found to be statistically greater (P < 0.05) than background grey matter readings in the agranular cortices, the frontal, hindlimb, parietal 1 and 2 cortices, and the hippocampus and dentate gyrus, excluding the pyramidal and granular cell layers. Density measurements taken in forelimb and hindlimb cortical regions correlate with forelimb and hindlimb recovery in foot-fault and beam balance tests (P < 0.05). We interpret these data to indicate neuronal membrane remodeling as a result of the disruption of neuronal membranes due to the impact and shearing forces associated with the FPI. The disruption and remodeling of neuronal membranes are in areas that are consistent with the loss and recovery of locomotor and spatial behavior as a result of FPI.