Characterization of Bax and Bcl-2 in apoptosis after experimental traumatic brain injury in the rat.

This study was undertaken to fulfill the need for additional data on the dynamics of Bax and Bcl-2 expression in conjunction to the cell death that ensues following experimental brain contusion. Adult Sprague-Dawley rats were subjected to a unilateral experimental controlled cortical contusion and killed at 1, 2, 4, 6 and 10 days post injury (dpi). Cell death was examined by the terminal deoxynucleotidyl transferase-mediated nick end labeling (TUNEL) method together with immunohistochemistry for cellular markers. Expression of Bax and Bcl-2 were analyzed by immunohistochemistry and in situ hybridization. The number of TUNEL-positive cells was highest at 1 dpi and decreased with time. At all time points, 10-16% of the TUNEL-positive cells showed an apoptotic nuclear morphology. The apoptotic features were restricted to neurons and some inflammatory cells. Immunohistochemistry for Bax revealed a translocation of Bax from a diffuse to a granular distribution in neurons. An up-regulation of Bax mRNA at 6 dpi was discernible. This increase was associated with a statistically significant increase in number of cells with up-regulated and translocated Bax protein. Moreover, a statistically significant increase of Bcl-2 mRNA was detected at 10 dpi. The potential window for anti-apoptotic treatment to salvage neurons is wide. The susceptibility of neurons to necrosis and apoptosis through different pathways during a prolonged post-traumatic period indicate that different pharmacological strategies may be required at different time points after trauma.