Apoptosis after traumatic human spinal cord injury

Object. Apoptosis is a form of programmed cell death seen in a variety of d evelopmental and disease states, including traumatic injuries. The main obj ective of this study was to determine whether apoptosis is observed after h uman spinal cord injury (SCI). The spatial and temporal expression of apopt otic cells as well as the nature of the cells involved in programmed cell d eath were also investigated. Methods. The authors examined the spinal cords of 15 patients who died betw een 3 hours and 2 months after a traumatic SCI. Apoptotic cells were found at the edges of the lesion epicenter and in the adjacent white matter, part icularly in the ascending tracts, by using histological (cresyl violet, hem atoxylin and eosin) and nuclear staining (Hoechst 33342). The presence of a poptotic cells was supported by staining with the terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick-end labeling technique and confirmed by immunostaining for the processed form of caspase-3 (CPP-32 ), a member of the interleukin-lp-converting enzyme/Caenorhabditis elegans D 3 (ICE/CED-3) family of proteases that plays an essential role in program med cell death. Apoptosis in this series of human SCIs was a prominent path ological finding in 14 of the 15 spinal cords examined when compared with f ive uninjured control spinal cords. To determine the type of cells undergoi ng apoptosis, the authors immunostained specimens with a variety of antibod ies, including glial fibrillary acidic protein, 2',3'-cyclic nucleotide 3'- phosphohydrolase (CNPase), and CD45/68. Oligodendrocytes stained with CNPas e and a number of apoptotic nuclei colocalized with positive staining for t his antibody. Conclusions. These results support the hypothesis that apoptosis occurs in human SCIs and is accompanied by the activation of caspase-3 of the cystein e protease family. This mechanism of cell death contributes to the secondar y injury processes seen after human SCI and may have important clinical imp lications for the further development of protease inhibitors to prevent pro grammed cell death.