Expression of Fas and Fas ligand after experimental traumatic brain injuryin the rat

Apoptotic cell death plays an important role in the cascade of neuronal deg eneration after traumatic brain injury (TBI), but the underlying mechanisms are not fully understood. However, increasing evidence suggests that expre ssion of Fas and its ligand (FasL) could play a major role in mediating apo ptotic cell death in acute and chronic neurologic disorders. To further inv estigate the temporal pattern of Fas and Fast expression after experimental TBI in the rat, male Sprague Dawley rats were subjected to unilateral cort ical impact injury. The animals were killed and examined for Fas and FasL p rotein expression and for immunohistologic analysis at intervals from 15 mi nutes to 14 days after injury. Increased Fas and FasL immunoreactivity was seen in the cortex ipsilateral to the injury site from 15 minutes to 72 hou rs after the trauma, respectively. Immunohistologic investigation demonstra ted a differential pattern of Fas and FasL expression in the cortex, respec tively: increased Fas immunoreactivity was seen in cortical astrocytes and neurons from 15 minutes to 72 hours after the injury. In contrast, increase d expression of FasL was seen in cortical neurons, astrocytes, and microgli a from 15 minutes to 72 hours after impact injury. Concurrent double-labeli ng examinations using terminal deoxynucleotidyl tranferase-mediated deoxyur idine-biotin nick end labeling identified Fas- and FasL-immunopostive cells with high frequency in the cortex ipsilateral to the injury site. In contr ast, there was no evidence of Fas- and FasL-immunopositive cells in the hip pocampus ipsilateral to the injury site up to 14 days after the trauma. Fur ther, Fas and Fast immunoreactivity was absent in the contralateral cortex and hippocampus at all time points investigated. These results reveal induc tion of Fas and Fast expression in the cortex after TBI in the rat. Further , these data implicate an involvement of Fas and Fast in the pathophysiolog ic mechanism of apoptotic neurodegeneration after TBI. Last, these data sug gest that strategies aimed to repress posttraumatic Fas- and Fast-induced a poptosis may open new perspectives for the treatment of TBI.