Regional expression of Par-4 mRNA and protein after fluid percussion braininjury in the rat

Regional levels of prostate apoptosis response-4 (Par-4) protein and mRNA w ere measured after lateral fluid percussion (FP) brain injury in rats. Immu nochemical studies indicated that Par-4 immunoreactivity (ir) is present in cortical neurons and hippocampal CA1-CA3 pyramidal neurons in uninjured ra ts. Increases of Par-4-ir were observed in the CA3 neurons of the ipsilater al hippocampus (IH), but not in injured left cortex (IC) at 48 h after FP b rain injury. Levels of the Par-4 mRNA measured by RT-PCR assay and protein measured by Western blot procedure were significantly increased in the inju red IC and IH, but not in the contralateral right cortex and hippocampus af ter brain injury. Levels of both Par-4 protein and mRNA were significantly increased in the IC and IH as early as 2 h and stayed elevated at 24 and 48 h after injury. These data show that the induction of proapoptotic Par-4 m RNA and protein occurs only in the IC and IH that have been observed to und ergo apoptosis and neuronal cell loss after lateral FP brain injury. Becaus e increased expression of Par-4 has been observed to contribute to apoptosi s and cell death in cultured neurons, the present temporal pattern of Par-4 expression is consistent with a role for Par-4 in apoptosis and neuronal c ell death after traumatic brain injury. (C) 2001 Academic Press.