Objective:To investigate the neuroprotective effect and mechanism of selenocysteine(SeC) on transient focal cerebral ischemia/reperfusion(tFCI/R) injury in mice.Methods:A tFCI/R model was established in Kunming mice after 1 hour of middle cerebral artery occlusion. Forty mice qualified for surgery were screened by doppler blood flow monitoring and neurological function defect score, and were randomly assigned to the SeC treatment group and the tFCI/R control group, while another 20 mice were selected as the Sham operation control group (underwent the whole operation without middle cerebral artery obstruction). Mice in SeC treatment group were given SeC solution intraperitoneal injection (2 mg/30 g) once at 0 h, 24 h and 48 h after surgery, and mice in the tFCI/R group and Sham group were injected with the same amount of saline in the same manner. At 24 h, 48 h and 72 h after surgery, 6 mice were randomly selected from each group for neurological impairment score and neurobehavioral test. Then the volume of cerebral infarction was measured by TTC staining, the degree of cerebral edema was measured by wet-dry weight method, the apoptosis of neurons was observed by Tunel-DAPI staining, the activity of caspase-3 and PARP were detected by Western blot, and the expressions of GSH and GSH-PX in mouse brain tissues were detected.Results:The Zea Longa scores of tFCI/R group((3.67±0.52), (3.33±0.52), (2.17±0.41) points) at 24h, 48h and 72h after surgery were significantly higher than that of Sham group((0.50±0.55), (0.67±0.52), (0.33±0.52)) ( t=10.26, 8.86, 6.81, all P<0.05). The scores of SeC treatment group ((2.50±0.55), (1.67±0.82), (0.83±0.75)) were significantly lower than that of tFCI/R group ( t=3.79, 4.19, 3.84, all P<0.05). The behavioral assessment results were consistent with the Zea Longa score. TTC experiment 72 h after surgery showed that no infarction lesion was formed in Sham group. Compared with tFCI/R group ((24.69±2.25)%), SeC treatment group ((11.89±1.64)%) had significantly reduced cerebral infarction volume, and the difference was statistically significant ( t=10.28, P<0.05). Wet-dry weight measurement showed that compared with Sham group, the moisture content ((85.87±1.36)%) of left brain tissue in tFCI/R group increased significantly ( t=8.73, P<0.05), the water content of left brain tissue in SeC treatment group ((81.06±1.07)%) decreased compared with tFCI/R group, and the difference was statistically significant ( t=6.22, P<0.05). Tunel-DAPI staining and Western blot results showed that SeC treatment significantly down-regulated the cleavage of caspase-3 and PARP, thus inhibiting neuronal apoptosis. GSH content in brain tissue was significantly increased in SeC treatment group ((85.83±1.46)%) compared with tFCI/R group ((64.69±2.15)%), and the difference was statistically significant ( t=18.19, P<0.05). The activity of GSH-PX in brain tissue was significantly increased in the SeC treatment group ((49.12±1.13)%)compared with the tFCI/R group ((38.74±1.93)%), and the difference was statistically significant ( t=10.38, P<0.05). Conclusion:SeC plays an effective neuroprotective role in tFCI/R-induced brain injury by inhibiting oxidative stress and apoptosis, which confirms the potential application value of SeC in the prevention and treatment of stroke.