The role of neuronal apoptosis inhibitor protein in a murine model of traumatic brain injury.

Abstract

In models of cell death, the IAPs prevent apoptosis through inhibition of caspases. We postulated that overexpression of NAIP would attenuate apoptosis and improve neurological recovery in a murine model of TBI by inhibiting caspase-3. TBI was performed using a weight drop model. Apoptosis was demonstrated in the cerebral cortex using the ISEL stain on brain sections and PCR amplification of fragmented DNA. The number of apoptotic cells in the cerebral cortex was significantly increased post TBI and the cell types undergoing apoptosis were identified by immunofluorescence as neurons and oligodendrocytes. Immunofluorescence and Western blot techniques were used to reveal that apoptosis was accompanied by a decrease in Naip and an increase in caspase-3 expression. We demonstrate that overexpression of NAIP attenuated DNA fragmentation through the inhibition of caspase-3 using ISEL and Western blot procedures. We were unable to show that NAIP overexpression improved neurological recovery following TBI using the Morris water maze neurological score. Overall, the data presented in this study provide evidence for a role of NAIP in inhibiting apoptosis following TBI.