Neural progenitor cells (NPCs) have been shown to be a promising
therapy for cell replacement and gene transfer in neurological diseases including
traumatic brain injury (TBI). However, NPCs often survive poorly after
transplantation despite immunosuppression, and the mechanisms of graft cell death are unknown. In this study, we evaluated
caspase- and
calpain-mediated mechanisms of cell death of neonatal mouse C17.2 progenitor cells, transplanted at 24 h following lateral fluid percussion
brain injury (FP) in rats. Adult Male Sprague-Dawley rats (
n = 30) were subjected to lateral FP injury (n = 18) or
sham surgery (n = 12). C17.2 cells labeled with green
fluorescent dye (
CMFDA) were engrafted in the perilesional deep cortex, and animals were sacrificed at 24 h, 72 h and 1 week post-
transplantation. Pro-apoptotic
caspase-mediated cleavage products (Ab246) and
calpain-mediated cleavage products (Ab38) were detected in the engrafted cells using immunohistochemistry. Only 2 to 4.5% of grafted NPCs were found to survive at 24 h post-
transplantation, regardless of injury status of the host brain, although brain-injured animals had significantly fewer graft cells than
sham-injured animals. Limited
caspase and
calpain-mediated graft cell death was observed in both
sham- and brain-injured animals, and
caspase-mediated graft cell death was significantly greater than
calpain-mediated graft cell death in all animals. Brain-injured animals had significantly increased
caspase-mediated graft cell death compared to
sham-injured animals. These results suggest that both the
caspase and
calpain family of
proteases are involved in graft cell death, and that
caspase-mediated apoptotic graft cell death predominates in the acute post-traumatic period following TBI.