The purpose of this study was to investigate the effects of edaravone on nitric oxide (NO) production, hydroxyl radical (OH⁻) metabolism, and neuronal nitric oxide synthase (nNOS) expression during cerebral ischemia and reperfusion.

Edaravone (3 mg/kg) was administered intravenously to 14 C57BL/6 mice just before reperfusion. Eleven additional mice received saline (controls). NO production and OH⁻ metabolism were continuously monitored using bilateral striatal in vivo microdialysis. OH⁻ formation was monitored using the salicylate trapping method. Forebrain ischemia was produced in all mice by bilateral occlusion of the common carotid artery for 10 minutes. Levels of NO metabolites, nitrite (NO₂⁻) and nitrate (NO₃⁻), were determined using the Griess reaction. Brain sections were immunostained with an anti-nNOS antibody and the fractional area density of nNOS-immunoreactive pixels to total pixels determined.

Blood pressure and regional cerebral blood flow were not significantly different between the edaravone and control groups. The levels of NO₂⁻ did not differ significantly between the 2 groups. The level of NO₃⁻ was significantly higher in the edaravone group compared with the control group after reperfusion. 2,3-dihydroxybenzoic acid levels were lower in the edaravone group compared with those in the control group after reperfusion. Immunohistochemistry showed nNOS expression in the edaravone group to be significantly lower than that in the control group 96 hours after reperfusion.

These in vivo data indicate that edaravone may have a neuroprotective effect by reducing levels of OH⁻ metabolites, increasing NO production and decreasing nNOS expression in brain cells.