Fluoxetine mitigating late-stage cognition and neurobehavior impairment induced by cerebral ischemia reperfusion injury through inhibiting ERS-mediated neurons apoptosis in the hippocampus.

Existing evidence from clinical and animal experiments all indicated that fluoxetine, selective serotonin-reuptake inhibitor (SSRI) and anti-depressant drug, has neuroprotection and improve functional outcomes after stroke. Endoplasmic reticulum stress (ERS) inducing apoptosis after cerebral ischemia reperfusion injury was demonstrated in our previous work. This trial was examined whether fluoxetine mitigates ERS-induced neuron apoptosis. Male sprague-dawley rats of cerebral ischemia reperfusion injury was produced via middle cerebral artery occlusion (MCAO) strategy, with ischemia for 90 min and reperfusion for 24 h. Experimental groups were divided into sham group, MCAO group, and fluoxetine group. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was used to evaluate cerebral infarct size. The expression of glucose-regulated protein 78 (GRP78), caspase-12, CHOP and caspase-3 were measured by Western blot and immunohistochemistry staining assays. Neurons apoptosis rate in the hippocampus was examined by the TUNEL assay. Neurobehavior examination was used to evaluate the motor function and passive avoidance test was used to assess cognition dysfunction. Fluoxetine treatment reduced the infarct size of rats after cerebral ischemia reperfusion injury. Furthermore, fluoxetine treatment decreased the expression of GRP-78, caspase-12, CHOP and caspase-3, and attenuated neurons apoptosis. Administration of fluoxetine promoted the damaged motor function. In the cognition test, after 4 days of fluoxetine treatment, cognition function of rats was improved. Fluoxetine treatment can mitigate cognition and neurobehavior impairment induced by cerebral ischemia reperfusion injury through inhibiting ERS-mediated neurons apoptosis in the hippocampus.