Lack of evidence for apoptosis as a cause of delayed onset paraplegia after spinal cord ischemia in rabbits.
The mechanisms for delayed onset paraplegia after transient spinal cord ischemia are not fully understood. We investigated whether apoptotic motor neuron death is involved in its development. Spinal cord ischemia was induced for 15 min by occlusion of the abdominal aorta in rabbits. At 8, 24, or 48 h after reperfusion, hind limb motor function was assessed, and the lumbar spinal cord was examined morphologically (hematoxylin-eosin and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick-end labeling staining) and biochemically (breakdown products of alpha-fodrin and patterns of DNA changes). At each time point, 14 rabbits were studied (7 for histopathology and 7 for biochemical analysis). Six rabbits served as sham controls. Delayed motor dysfunction developed in two thirds of the rabbits. The motor neurons in the rabbits with motor dysfunction (not paraplegia) showed swelling and a finely granular dispersed Nissl substance. In paraplegic rabbits, destruction of the gray matter and prominent inflammatory cell infiltration were observed. No apoptotic motor neuron was found in any rabbit. There was neither detectable increase in a caspase-3-mediated breakdown product of alpha-fodrin, nor DNA laddering in any rabbit. The results suggest that apoptosis has a negligible role in the pathophysiology of delayed paraplegia in the spinal cord ischemia model examined.


CONCLUSIONS
Although the possibility of apoptotic motor neuron death cannot be completely excluded, delayed onset paraplegia after transient spinal cord ischemia is largely associated with necrotic cell death.
Warner
David S
DS
Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Japan.
Kiyoshima
Takashi
T
Fukuda
Shiro
S
Matsumoto
Mishiya
M
Iida
Yasuhiko
Y
Oka
Satoe
S
Nakakimura
Kazuhiko
K
Sakabe
Takefumi
T
D000758:Anesthesia; D018685:Anesthetics, Inhalation; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001784:Blood Gas Analysis; D001794:Blood Pressure / Q000502:physiology; D001831:Body Temperature / Q000502:physiology; D002352:Carrier Proteins / Q000378:metabolism; D053938:DNA Fragmentation; D004591:Electrophoresis, Polyacrylamide Gel; D005071:Evoked Potentials / Q000502:physiology; D020287:In Situ Nick-End Labeling; D007530:Isoflurane; D008840:Microfilament Proteins / Q000378:metabolism; D010264:Paraplegia / Q000209:etiology*; D011817:Rabbits; D013056:Spectrophotometry, Ultraviolet; D013116:Spinal Cord / Q000378:metabolism; D020760:Spinal Cord Ischemia / Q000150:complications* / Q000378:metabolism / Q000473:pathology*; D013049:Spectrin
D018685:Anesthetics, Inhalation; D002352:Carrier Proteins; D007530:Isoflurane; D008840:Microfilament Proteins; D013049:Spectrin