Epidemiological studies have demonstrated that
vitamin C decreases the risk of
stroke, which has generally been ascribed to its function as
antioxidant and
free radical scavenger. However, whether there is a defined molecular target for
vitamin C on
stroke is unknown. Utilizing
middle cerebral artery occlusion (MCAO) in rats as a model for
ischemic stroke, we demonstrated that long-term, low-dose administration of
vitamin C prior to MCAO could exert significant
neuroprotective effect on the brain damage. The long-term, low-dose
vitamin C pretreated rats had decreased
brain infarct size and decreased neurological deficit score compared with the vehicle or single high dose pretreated MCAO rats. Furthermore, electrophysiological experiments using patch clamp technique showed that
vitamin C increased the whole-cell current of the large-conductance Ca2+-activated K+ (BKCa) channel. Moreover,
vitamin C increased the open probability of the channel without change its amplitude. Importantly, blockade of the BKCa channels abolished the
neuroprotective effect of
vitamin C on MCAO. Therefore, this study shows that long-term, low-dose pretreatment with
vitamin C could reduce MCAO-induced brain damage through activation of the BKCa channels, suggesting that the BKCa channel is a molecular target of
vitamin C on
stroke.