The alterations of bcl-x-L and bax mRNA expression following traumatic brain injury in rats

Objective To investigate the alterations of bcl-2 gene family in the rat brain and the molecular mechanism of neuronal apoptosis following traumatic brain injury. Methods Male Sprague-Dawley rats were subjected to lateral fluid perfusion brain injury(FPI) of moderate severity. bcl-x L and bax mRNA expression was detected by RT-PCR. In addition to morphological evidence of apoptosis, TUNEL histochemistry was used to identify DNA fragmentation in situ at both light and electron microscopic levels, the characteristic internucleosomal DNA fragmentation of apoptosis was demonstrated by DNA gel electrophoresis. Results The apoptotic response to trauma was regionally distinct and might be involved in both acute and delayed patterns of cell death. bcl-x L mRNA decreased in the ipsilateral hemisphere to the impact site 6 h after injury (67.42%±7.54%, P 0.01). The decrease in bcl-x L mRNA preceded apoptosis, which was observed 24h after injury. This was the main cause of down-regulation of the ratio of bcl-x to bax in the acute period (minutes to hours) following lateral fluid perfusion brain injury. bax mRNA was observed to rise slowly , doubling at 3rd day after injury, then returned to the sham level slowly. The delayed cell death (days to weeks) involved the up-regulation of pro-apoptotic gene bax. Conclusions The decreased expression of bcl-x L mRNA and increased expression of bax mRNA coincide with apoptosis following brain injury. The bcl-2 gene family is involved in neuronal apoptosis after TBI, and the mRNA expression alterations of the family members lead the neuronal cells to apoptosis.