Neuroprotective effects of edaravone, a free radical scavenger, on the rat hippocampus after pilocarpine-induced status epilepticus.
OBJECTIVE
Edaravone (MCI-186) is a newly developed antioxidative radical scavenger for the treatment of acute cerebral infarction, exerting neuroprotective effects against ischemic insult. The neuroprotective effects of edaravone on pilocarpine-induced seizures in rats were investigated.


METHODS
Rats were treated intraperitoneally with saline or edaravone (1-30 mg/kg), applied 30 min before pilocarpine hydrochloride (330 mg/kg). The onset of status epilepticus (SE) and mortality were recorded for a period of at least 3 days. The cell loss and immunoreactivities of nitric oxide synthase (NOS) in the hippocampus from control and the day 3 rats after SE, treated with saline or edaravone, were evaluated.


RESULTS
Edaravone (1mg/kg) significantly prevented cell loss in the hippocampus after SE while easier inducing SE. The higher dose of drug could not induce SE significantly but tended to increase the rate of mortality. Inducible NOS (iNOS) expression was significantly decreased in the hippocampus from day 3 rats treated with 1mg/kg edaravone, compared with saline group, while neuronal NOS (nNOS) and iNOS significantly increased in the hippocampus treated with saline, compared with control group. Significant alteration of endothelial NOS (eNOS) expression in the hippocampus among control group, saline group, and edaravone group was not shown.


CONCLUSIONS
Edaravone may act as a neuroprotector for the hippocampus after SE by reducing at least iNOS although the low dose of drug easier induces SE because of preventing an endogenous antiepileptic effect of NO.
Kamida
T
T
Department of Neurosurgery, Oita University, Faculty of Medicine, 1-1 Idaigaoka, Hasama-machi, Oita 879-5593, Japan. kamida@med.oita-u.ac.jp
Fujiki
M
M
Ooba
H
H
Anan
M
M
Abe
T
T
Kobayashi
H
H
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D002452:Cell Count / Q000379:methods; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D000077553:Edaravone; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010862:Pilocarpine; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D013226:Status Epilepticus / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control*; D013997:Time Factors
D018696:Neuroprotective Agents; D010862:Pilocarpine; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D000077553:Edaravone; D000983:Antipyrine