Cell-specific DNA fragmentation may be attenuated by a survivin-dependent mechanism after traumatic brain injury in...

Survivin attenuates apoptosis by inhibiting cleavage of some cell proteins by activated caspase-3. We recently discovered strong up-regulation of survivin, primarily in astrocytes and a sub-set of neurons, after traumatic brain injury (TBI) in rats. In this study we characterized co-expression of survivin with activated caspase-3 and downstream DNA fragmentation (TUNEL) in astrocytes and neurons after TBI. Western blot analysis revealed significant time-dependent increases in active caspase-3 between 5 and 14 days post-injury. No difference was observed between the proportion of survivin-positive and survivin-negative cells labeled with active caspase-3 at 5 or 7 days post-injury, as indicated by dual fluorescent immunostaining. Labeling of survivin-negative cells with TUNEL was, however, significantly greater than for survivin-positive cells, suggesting that expression of survivin may attenuate DNA cleavage and progression of apoptosis. A higher proportion of astrocytes than neurons accumulated active caspase-3. In contrast, co-localization with TUNEL was significantly higher for neurons than for astrocytes. These data suggest that survivin expression may attenuate DNA cleavage and cell death, and that this mechanism operates in a cell type-specific manner after TBI.