NEURONAL AND GLIAL APOPTOSIS AFTER TRAUMATIC SPINAL-CORD INJURY

Cell death was examined by studying the spinal cords of rats subjected to traumatic insults of mild to moderate severity. Within minutes aft er mild weight drop impact (a 10 gm weight falling 6.25 mm), neurons i n the immediate impact area showed toss of cytoplasmic Nissl substance s. Over the next 7 d, this lesion area expanded and cavitated. Termina l deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphat e-biotin nick end labeling (TUNEL)-positive neurons were noted primari ly restricted to the gross lesion area 4-24 hr after injury, with. a m aximum presence at 8 hr after injury. TUNEL-positive glia were present at all stages studied between 4 hr and 14 d, with a maximum presence within the lesion area 24 hr after injury. However 7 d after injury, a second wave of TUNEL-positive glial cells was noted in the white matt er peripheral to the lesion and extending at least several millimeters away from the lesion center. nle suggestion of apoptosis was supporte d by electron microscopy, as well as by nuclear staining with Hoechst 33342 dye, and by examination of DNA prepared from the lesion site. Fu rthermore, repeated intraperitoneal injections of cycloheximide, begin ning immediately after a 12.5 mm weight drop insult, produced a substa ntial reduction in histological evidence of cord damage and in motor d ysfunction assessed 4 weeks later. Present data support the hypothesis that apoptosis dependent on active protein synthesis contributes to t he neuronal and glial cell death, as well as to the neurological dysfu nction, induced by mild-to-moderate severity traumatic insults to the rat spinal cord.