Cell-specific upregulation of survivin after experimental traumatic brain injury in rats.

Abstract

In this study, we examined the expression and cellular localization of survivin and proliferating cell nuclear antigen (PCNA) after controlled cortical impact traumatic brain injury (TBI) in rats. There was a remarkable and sustained induction of survivin mRNA and protein in the ipsilateral cortex and hippocampus of rats after TBI, peaking at five days post injury. In contrast, both survivin mRNA and protein were virtually undetectable in craniotomy control animals. Concomitantly, expression of PCNA was also significantly enhanced in the ipsilateral cortex and hippocampus of these rats with similar temporal and spatial patterns. Immunohistochemistry revealed that survivin and PCNA were co-expressed in the same cells and had a focal distribution within the injured brain. Further analysis revealed a frequent co-localization of survivin and GFAP, an astrocytic marker, in both the ipsilateral cortex and hippocampus, while a much smaller subset of cells showed co-localization of survivin and NeuN, a mature neuronal marker. Neuronal localization of survivin was observed predominantly in the ipsilateral cortex and contralateral hippocampus after TBI. PCNA protein expression was detected in both astrocytes and neurons of the ipsilateral cortex and hippocampus after TBI. Collectively these data demonstrate that the anti-apoptotic protein survivin, previously characterized in cancer cells, is abundantly expressed in brain tissues of adult rats subjected to TBI. We found survivin expression in both astrocytes and a sub-set of neurons. In addition, the expression of survivin was co-incident with PCNA, a cell cycle protein. This suggests that survivin may be involved in regulation of neural cell proliferative responses after traumatic brain injury.