A multicenter randomized clinical trial demonstrated that
acute ischemic stroke patients treated with
edaravone, a scavenger of
hydroxyl radicals, had significant functional improvement. We tested the hypothesis that
edaravone has protective effects against white matter lesions (WML) and endothelial injury, using a rat chronic hypoperfusion model. Adult Wistar rats underwent
ligation of bilateral common carotid artery (LBCCA) and were divided into the
edaravone group (injected once only immediately after LBCCA [n=39, ED(1)]; and injected on three consecutive days [n=39, ED(3)]), the vehicle group (n=39), and the
sham group (n=15). Cerebral blood flow, Morris water maze performance, footprint test for locomotor function, immunohistochemical analyses and Western blot analysis were performed before and after LBCCA. The ED(3) group upregulated
endothelial nitric oxide synthase and attenuated
Evans Blue extravasation at day 3 after LBCCA (P<0.05).
Edaravone markedly suppressed accumulation of 4-hydroxy-2-nonenal-modified
protein and 8-hydroxy-deoxyguanosine (P<0.01), and loss of oligodendrocytes (P<0.05) in the cerebral white matter at days 3, 7, 14, 21 and 28 after LBCCA. These results were more evident in the ED(3) group. Moreover, at day 21 after LBCCA, spatial memory but not motor function, and axonal damage were significantly improved by three-time treatment of
edaravone (P<0.05). Our results indicated that 3-day treatment with
edaravone provides protection against WML through endothelial protection and
free radical scavenging and suggested that
edaravone is potentially useful for the treatment of
cognitive impairment.