Effect of a free radical scavenger, edaravone, on free radical reactions: related signal transduction and cerebral vasospasm in the rabbit subarachnoid hemorrhage model.
OBJECTIVE
it is hypothesized that free radical reactions evoked by oxyhemoglobin (oxyHb) cause cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH), even though the detailed mechanisms have not yet been fully established. The aims of this study were thus to investigate, through the use of the double-hemorrhage rabbit model, the possibility that free radical reactions play a role in cerebral vasospasm and to delineate the mechanism of signal transduction that causes cerebral vasospasm.


METHODS
in the SAH group, SAH was simulated using the double-hemorrhage rabbit model. In the treatment group, edaravone (0.6 mg/kg), a potent free radical scavenger, was injected into the central ear vein twice a day. Four days after SAH, the basilar artery was excised. The degree of cerebral vasospasm was evaluated by measuring the diameter of each basilar artery, and the expression of Rho-kinase in the vascular wall was examined by western blotting.


RESULTS
the diameter of the basilar artery in the edaravone-treated group was 0.64 ± 0.06 mm, which was statistically significantly larger than that in the nontreated SAH group (0.50 ± 0.03 mm; p < 0.01). The expression of Rho-kinase in the edaravone-treated group was statistically significantly reduced in comparison to that of the nontreated SAH group.


CONCLUSIONS
results from this study have indicated for the first time that free radical reactions mediated by oxyHb may play an important role in the pathogenesis of cerebral vasospasm through the expression of Rho-kinase.
Department of Neurosurgery, Hirosaki University School of Medicine, Hirosaki, Japan.
Akira
A
Munakata
Hiroki
H
Ohkuma
Norihito
N
Shimamura
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D001488:Basilar Artery / Q000187:drug effects / Q000473:pathology; D004195:Disease Models, Animal; D000077553:Edaravone; D016166:Free Radical Scavengers / Q000494:pharmacology* / Q000627:therapeutic use; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D007275:Injections, Intravenous / Q000379:methods; D011817:Rabbits; D013345:Subarachnoid Hemorrhage / Q000150:complications; D020301:Vasospasm, Intracranial / Q000188:drug therapy / Q000201:enzymology* / Q000209:etiology / Q000473:pathology; D054460:rho-Associated Kinases / Q000378:metabolism*
D016166:Free Radical Scavengers; D054460:rho-Associated Kinases; D000077553:Edaravone; D000983:Antipyrine