OBJECTIVE : Recently, microRNAs (miRs) have been reported to be novel regulators in ischemic stroke. In this study, we investigated the pattern of miR-451 expression along with its clinical application in human ischemic stroke and in an in vivo mouse model. METHODS : The level of miR-451 was evaluated in patients and mice after ischemic stroke. National Institute of Health Stroke Scale scores and brain infarct volume were analyzed to the correlation of miR-451 expression and clinical information. In addition, blood samples and brain tissues were collected from an established middle cerebral artery occlusion model consisting of 12 adult male mice at 24 hours after the middle cerebral artery occlusion. RESULTS : The results showed that miR-451 levels in the circulating blood of ischemic stroke patients were greatly decreased compared with the control. Further correlation analysis revealed a negative association between miR-451 and National Institute of Health Stroke Scale scores (r = -0.6104, P < 0.001) and infarct volume (r = -0.5442, P < 0.001). Moreover, miR-451 was down-regulated in response to middle cerebral artery occlusion in vivo, along with a negative correlation between miR-451 in brain and blood (r = 0.9240, P < 0.01). In addition, forced expression of miR-451 weakened ischemic brain infarction and apoptosis levels in focal ischemia-stroked mice, while downregulation of miR-451 significantly augmented ischemic injury. CONCLUSIONS : In conclusion, miR-451 displays the neuroprotective effect in ischemic stroke and might serve as a novel therapeutic target of ischemic stroke.