Objective：To determine the neuroprotective effect and mechanism of the stress-induced protein Sestrin2 in focal ischemic cerebral injury in rats. Methods：A clinically relevant Sprague-Dawley rat model of focal ischemic brain injury was established by photochemical embolization. Rats were divided into control group，model group，negative virus group，and Sesn2 overexpression group. Sestrin2 expression was upregulated using gene overexpression technique. The neurological deficits of each group were scored accord－ing to the modified Longa’s neurological scoring system. Cerebral infarction volume and neuronal injury were measured by TTC and Nissl staining，respectively. Sesn2 and VEGF protein expression was measured by Western blot. Results：Neurological function scores were significantly decreased in the Sesn2 overexpression group（2.100±0.738） than in the model group（3.200±0.789） and negative virus group（3.200±0.632）（both P<0.05）. TTC staining showed that cerebral infarction volume was significantly smaller in the Sesn2 overexpression group（0.034±0.004） than in the model group（0.072±0.003） and negative virus group（0.069±0.003）（both P<0.05）. In addition，Nissl staining showed that the number of intact neurons was significantly higher in the Sesn2 overexpression group（334.300±21.550） than in the model group（122.000±17.000） and negative virus group（137.700±16.070）（both P<0.05）. Western blot analysis indicated that Sesn2 and VEGF protein expression was significantly upregulated in the Sesn2 overexpression group than in the model group（0.542±0.035 and 1.074±0.094，respectively） and negative virus group（0.578±0.052 and 1.196±0.167，respectively）（all P<0.05）. Conclusion：Sesn2 overex－pression improves neurological deficit，decreases cerebral in－farction，and reduces neuronal damage. This protective effect may be mediated by upregulating VEGF and promoting mi－crovascular regeneration in areas of cerebral ischemia.
