Protective effects of cold spinoplegia with fasudil against ischemic spinal cord injury in rabbits.
OBJECTIVE
Paraplegia remains a serious complication after surgical repair of thoracoabdominal aortic aneurysms. The aim of this study was to evaluate the neuroprotective efficacy of fasudil, a Rho kinase (ROCK) inhibitor, by reducing the number of infiltrating cells in the ventral horn and increasing the induction of eNOS against ischemic spinal cord injury in rabbits.


METHODS
Eighteen Japanese white rabbits were divided into three groups: saline (group 1, n = 7, 4 degrees C) and fasudil (group 2, n = 6, 4 degrees C) were immediately infused into the isolated segmental lumbar arteries over 30 seconds after aortic clamping. Group 3 (n = 5) was the sham-operated group. Hind limb function was evaluated 4 and 8 hours, and 1 and 2 days after 15 minutes of transient ischemia. Cell damage was analyzed by hematoxylin and eosin staining and temporal profiles of endothelial nitric oxide synthase immunoreactivity were performed. The number of intact motor neuron cells and infiltrating cells in the ventral horn were compared.


RESULTS
Two days after reperfusion, group 2 and group 3 showed better neurologic function, a greater number of intact motor neuron cells, and a smaller number of infiltrating cells in the ventral horn than group 1. The induction of endothelial nitric oxide synthase (eNOS) was prolonged up to 2 days after reperfusion in group 2.


CONCLUSIONS
These results indicate that fasudil has neuroprotective effects against ischemic spinal cord injury in rabbits by reducing the number of infiltrating cells in the ventral horn and prolonging the expression of eNOS.
Department of Cardiovascular Surgery, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Hironori
H
Baba
Yoshihisa
Y
Tanoue
Taketoshi
T
Maeda
Mariko
M
Kobayashi
Shinichiro
S
Oda
Ryuji
R
Tominaga
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D000818:Animals; D000870:Anterior Horn Cells / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D001011:Aorta / Q000601:surgery; D003250:Constriction; D004195:Disease Models, Animal; D004790:Enzyme Induction; D007036:Hypothermia, Induced; D007150:Immunohistochemistry; D007261:Infusions, Intra-Arterial; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009460:Neurologic Examination; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis; D010264:Paraplegia / Q000201:enzymology / Q000517:prevention & control; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011817:Rabbits; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D020760:Spinal Cord Ischemia / Q000201:enzymology / Q000503:physiopathology / Q000517:prevention & control*; D013997:Time Factors; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D018696:Neuroprotective Agents; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D052250:Nitric Oxide Synthase Type III; D054460:rho-Associated Kinases; C049347:fasudil