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Objective: To investigate the effects of sodium ferulate (SF), an intravenous drug made from traditional Chinese herbs, on activation of postsynaptic density-95 (PSD-95) and neuroprotection after transient cerebral artery occlusion in rats. Methods: Forty-six male Sprague-Dawley rats were randomized into 2 groups (n=23 in each group): the control group and the SF group. After anesthesia, the middle cerebral artery occlusion (MCAO) was conducted with the intraluminal filament technique. The neurological deficit was assessed with the method devised by Bederson et al.8 The 2, 3, 4-triphenyltetrazolium chloride staining was used to assess the infarct volume. We adopted a modified six-point scale to conduct neurobehavioral evaluation. Immediately the activation of postsynaptic density-95 (PSD-95) was studied with West blot analysis system in the cortex and striatum of rat brain. Results: The neurologic deficit score of the SF group decreased substantially compared with that of the control group (P<0.05). The infarct volume of the control group (168.1 mm3 ± 42.2 mm3) was significantly larger than that of the SF group (61.5 mm3 ± 28.7 mm3) at 24 hours after reperfusion (P<0.01). And the rats showed some neurological deficit. The activity of PSD-95 in the SF group at most timepoints was less than that in the control group. No upregulation of PSD-95 protein could be detected in the contralateral cortex.Conclusions: Sodium ferulate can induce a neuroprotective effect against the transient focal cerebral ischemic injury and weaken the activation of PSD-95 in ischemic area after MCAO.