Neuronal apoptosis and necrosis following spinal cord ischemia in the rat.
We examined the characteristics of neuronal death induced by ischemia in the spinal cord. Spinal cord ischemia was induced in Long-Evans rats by occlusion of the descending aorta with a 2F Fogarty catheter for 20 min (model 1) or more limited aortic occlusion (15 min) coupled with blood volume reduction (model 2); rats were sacrificed 6 h-7 days later. The animals developed variable paraparesis in model 1 and reliable paraplegia in model 2. The extent of histopathological spinal cord damage, being maximal in the lumbar cord, correlated well with the severity of paraparesis. Two distinct types of spinal cord neuronal death were observed, consistent with necrosis and apoptosis. Neuronal necrosis was seen in gray matter laminae 3-7, characterized by the rapid (6 h) onset of eosinophilia on hematoxylin/eosin-stained sections, and gradual (1-7 days) development of eosinophilic ghosting. Although TUNEL positivity was present, disintegration of membranes and cytoplasmic organelles was seen under electron microscopy. Neuronal apoptosis was seen after 1-2 days in dorsal horn laminae 1-3, characterized by both TUNEL positivity and electron microscopic appearance of nuclear chromatin aggregation and the formation of apoptotic bodies. DNA extracted from the ischemic lumbar cord showed internucleosomal fragmentation (laddering) on gel electrophoresis. These data suggest that distinct spinal cord neuronal populations may undergo necrosis and apoptosis following transient ischemic insults.
Kato
H
H
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Kanellopoulos
G K
GK
Matsuo
S
S
Wu
Y J
YJ
Jacquin
M F
MF
Hsu
C Y
CY
Kouchoukos
N T
NT
Choi
D W
DW
D000818:Animals; D001012:Aorta, Abdominal; D017209:Apoptosis; D002466:Cell Nucleolus / Q000648:ultrastructure; D002467:Cell Nucleus / Q000648:ultrastructure; D004396:Coloring Agents; D003593:Cytoplasm / Q000648:ultrastructure; D053938:DNA Fragmentation; D006614:Hindlimb / Q000294:innervation; D007511:Ischemia / Q000473:pathology* / Q000503:physiopathology*; D008297:Male; D008854:Microscopy, Electron; D009043:Motor Activity; D009336:Necrosis; D009474:Neurons / Q000473:pathology* / Q000648:ultrastructure; D015388:Organelles / Q000473:pathology; D051381:Rats; D013116:Spinal Cord / Q000098:blood supply* / Q000473:pathology* / Q000503:physiopathology; D013997:Time Factors
D004396:Coloring Agents