Apoptotic and anti-apoptotic mechanisms following spinal cord injury

A number of studies have provided evidence that cell death from moderate tr aumatic spinal cord injury (SCI) is regulated, in part, by apoptosis that i nvolves the caspase family of cysteine proteases. However, little or no inf ormation is available about anti-apoptotic mechanisms mediated by the inhib itors of apoptosis (IAP) family of proteins that inhibit cell death pathway s. In the present study, we examined caspase and IAP expression in spinal c ords of rats subjected to moderate traumatic injury. Within 6 h after injur y, caspase-8 and-9 (2 initiators of apoptosis) were predominantly present i n gray matter neurons within the lesion epicenter. By 3 days following spin al cord injury (SCI), caspase-8 and-9 immunoreactivity was localized to gra y and white matter cells, and by 7 days following SCI, both upstream caspas es were expressed in cells within white matter or within foamy macrophages in gray matter. Caspase-3. an effector caspase. was evident in a few fragme nted cells in gray matter at 24 h following injury and then localized to wh ite matter in later stages. Thus, distinct patterns of caspase expression c an be found in the spinal cord following injury. XIAP, cIAP-1, and cIAP-2, members of the LAP family, were constitutively expressed in the cord. Immun oblots of spinal cord extracts revealed that the processed forms of caspase s-8 and-9 and cleavage of PARP are present as early as 6 h following trauma . The expression of caspases corresponded with the detection of cleavage of XIAP into 2 fragments following injury, cIAP-1 and cIAP-2 expression remai ned constant during early periods following SCI but demonstrated alteration s by 7 days following SCI. Our data are consistent with the idea that XIAP may have a protective role within the spinal cord, and that alteration in c leavage of XIAP may regulate cell death following SCI.