NEURONAL APOPTOSIS AND NECROSIS FOLLOWING SPINAL-CORD ISCHEMIA IN THERAT

We examined the characteristics of neuronal death induced by ischemia in the spinal cord. Spinal cord ischemia was induced in Long-Evans rat s by occlusion of the descending aorta with a 2F Fogarty catheter for 20 min (model 1) or more limited aortic occlusion (15 min) coupled wit h blood volume reduction (model 2); rats were sacrificed 6 h-7 days la ter. The animals developed variable paraparesis in model 1 and reliabl e paraplegia in model 2, The extent of histopathological spinal cord d amage, being maximal in the lumbar cord, correlated well with the seve rity of paraparesis. Two distinct types of spinal cord neuronal death were observed, consistent with necrosis and apoptosis. Neuronal necros is was seen in gray matter laminae 3-7, characterized by the rapid (6 h) onset of eosinophilia on hematoxylin/eosin stained sections, and gr adual (1-7 days) development of eosinophilic ghosting. Although TUNEL positivity was present, disintegration of membranes and cytoplasmic or ganelles was seen under electron microscopy. Neuronal apoptosis was se en after 1-2 days in dorsal horn laminae 1-3, characterized by both TU NEL positivity and electron microscopic appearance of nuclear chromati n aggregation and the formation of apoptotic bodies. DNA extracted fro m the ischemic lumbar cord showed internucleosomal fragmentation (ladd ering) on gel electrophoresis. These data suggest that distinct spinal cord neuronal populations may undergo necrosis and apoptosis followin g transient ischemic insults. (C) 1997 Academic Press.