MCI-186 prevents spinal cord damage and affects enzyme levels of nitric oxide synthase and Cu/Zn superoxide dismutase after transient ischemia in rabbits.
OBJECTIVE
The mechanism of spinal cord injury is believed to be related to the vulnerability of spinal motor neuron cells against ischemia. We tested whether MCI-186, which is useful for treating ischemic damage in the brain, can protect against ischemic spinal cord damage.


METHODS
After induction of ischemia, MCI-186 or vehicle was injected intravenously. Cell damage was analyzed by observing the function of the lower limbs and by counting the number of motor neurons. To investigate the mechanism by which MCI-186 prevents ischemic spinal cord damage, we observed the immunoreactivity of Cu/Zn superoxide dismutase, neuronal nitric oxide synthase, and endothelial nitric oxide synthase.


RESULTS
MCI-186 eased the functional deficits and increased the number of motor neurons after ischemia. The induction of neuronal nitric oxide synthase was significantly reduced by the treatment with MCI-186. Furthermore, the increase in the induction of endothelial nitric oxide synthase and Cu/Zn superoxide dismutase was more pronounced.


CONCLUSIONS
These results indicate that MCI-186 may protect motor neurons from ischemic injury by reducing neuronal nitric oxide synthase and increasing endothelial nitric oxide synthase. MCI-186 may be a strong candidate for use as a therapeutic agent in the treatment of ischemic spinal cord injury.
Takahashi
Goro
G
Department of Cardiovascular Surgery, Tohuko University Graduate School of Medicine, Sendai, Japan.
Sakurai
Masahiro
M
Abe
Koji
K
Itoyama
Yasuto
Y
Tabayashi
Koichi
K
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001707:Biopsy, Needle; D004195:Disease Models, Animal; D000077553:Edaravone; D007150:Immunohistochemistry; D007275:Injections, Intravenous; D007511:Ischemia / Q000201:enzymology / Q000517:prevention & control*; D008297:Male; D009046:Motor Neurons / Q000187:drug effects / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000032:analysis / Q000187:drug effects* / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I; D011817:Rabbits; D011897:Random Allocation; D012016:Reference Values; D012680:Sensitivity and Specificity; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000473:pathology* / Q000517:prevention & control*; D013482:Superoxide Dismutase / Q000187:drug effects* / Q000378:metabolism
D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D013482:Superoxide Dismutase; D000077553:Edaravone; D000983:Antipyrine