Effect of U—74389G on apoptosis and bcl—2 expression following traumatic brain injury in rats

Objective: To investigate the relationship between oxidative stress and apoptosis and bcl-2 expression fol-lowing traumatic brain injury (TBI). Methods: Male Sprague-Dawley ras were subjected to lateral fluid percussionbrain injury (FPBI) of moderate severity. U-74389G (20 mg/kg) were administered intravenously before FPBI. Theneurological functions were measured by beam-walk task (BWT) and beam-balance task (BBT). In addition to mor-phological evidence of apoptosis, TUNEL histochemistry was used to identify DNA fragmentation in situ with both lightand electron microscopic levels. The internucleosomal fragments of DNA in apoptotic cells were examined using agarose

Effect of U-74389G on apoptosis and bcl-2 expression following traumatic brain injury in rats

Objective: To investigate the relationship between oxidative stress and apoptosis and bcl-2 expression following traumatic brain injury (TBI). Methods: Male Sprague-Dawley rats were subjected to lateral fluid percussion brain injury (FPBI) of moderate severity. U-74389G (20 mg/kg) were administered intravenously before FPBI. The neurological functions were measured by beam-walk task (BWT) and beam-balance task (BBT). In addition to morphological evidence of apoptosis, TUNEL histochemistry was used to identify DNA fragmentation in situ with both light and electron microscopic levels. The internucleosomal fragments of DNA in apoptotic cells were examined using agarose gel electrophoresis. Bcl-2 protein expression was detected by immunohistochemistry. Results: The scores of BWT and BBT were significantly improved (P <0.01) in the treated animals. The treatment significantly reduced the number of apoptotic cells that was counted in the areas of the injured hemisphere at various time points following TBI. No DNA ladder was detected in the treated rats. Bcl-2 expression was observed in the cerebral cortex, subcortical white matter, dentate gyrus, hippocampal CA1 and CA3 region ipsilateral to injured hemisphere. Bcl-2 positive cells displayed normal nuclear morphology; Little Bcl-2 positive cells revealed morphological feature of apoptosis or necrosis. The immu-noreactivity of Bcl-2 protein decreased significantly in the hippocampus ipsilateral impact site as early as 6 h post-injury. During 1 - 3 d after injury, the bcl-2 protein expression decreased relatively slow. In the U-74389G treated groups, the downregulation of bcl-2 expression was halted. Conclusion: In this model, apoptosis is associated with an activation of lipid peroxidation. U-74389G may block oxidative stress and halt the downregulation of bcl-2 expression. These may be one of the molecular mechanisms of the neuro-protective effects by U-74389G.