The effects of cyclosporin A and insulin on ischemic spinal cord injury in rabbits.
We examined the effects of cyclosporin A (CsA), a drug that inhibits mitochondrial permeability transition pore, and insulin on ischemic spinal cord damage in rabbits. We assigned rabbits to 5 groups (n = 6 in each); sham barrier-opened group (sham BO), barrier-opened group (BO), barrier-opened-CsA group (BO-CsA), barrier-opened-insulin group (BO-I), and barrier-opened-CsA-insulin group (BO-CsA-I). The blood-spinal cord barrier was opened to facilitate drug penetration by a mild injury to the lumber spinal cord on day 1. CsA (10 mg/kg per day IV) was administered on day 3 to day 5 (total 30 mg/kg). Insulin was administered 30 min before ischemia. In all groups, spinal cord ischemia was produced on day 5 by occluding the abdominal aorta for 13 min. Neurological and histopathological evaluations were performed 4 days after ischemia. In group BO-CsA, blood glucose concentrations were significantly larger compared with the other four groups, and no protection was observed. In contrast, hindlimb motor function in groups BO-I and Bo-CsA-I and histopathology in group BO-CsA-I were significantly better than in groups sham BO, BO, and BO-CsA. The results indicate that insulin protects against ischemic spinal cord injury, whereas the effect of CsA is, at best, minimal.
Tsuruta
Shunsuke
S
Department of Anesthesiology-Resuscitology, Yamaguchi University School of Medicine, Yamaguchi, Japan.
Matsumoto
Mishiya
M
Fukuda
Shiro
S
Yamashita
Atsuo
A
Cui
Ying Jun
YJ
Wakamatsu
Hiroya
H
Sakabe
Takefumi
T
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D001921:Brain / Q000473:pathology; D002199:Capillary Permeability; D016572:Cyclosporine / Q000494:pharmacology*; D006614:Hindlimb / Q000502:physiology; D007328:Insulin / Q000494:pharmacology*; D008159:Lumbar Vertebrae; D033681:Mitochondrial Membrane Transport Proteins / Q000037:antagonists & inhibitors / Q000502:physiology; D000083162:Mitochondrial Permeability Transition Pore; D009068:Movement; D009474:Neurons / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010264:Paraplegia / Q000503:physiopathology; D011817:Rabbits; D013116:Spinal Cord / Q000098:blood supply; D013119:Spinal Cord Injuries / Q000503:physiopathology*; D020760:Spinal Cord Ischemia / Q000097:blood / Q000473:pathology / Q000503:physiopathology*
D001786:Blood Glucose; D007328:Insulin; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D018696:Neuroprotective Agents; D016572:Cyclosporine