Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Pharmacology and Toxicology

Stroke has grown to the fifth and third leading causes of death, respectively, in the U.S and the rest of the world. Vortioxetine (VTX) is a multimodal antidepressant agent that balances 5-HT receptors and represses the serotonin transporter.The purpose of this research was to investigate if VTX protects against cerebral ischemia induced by occluding the middle cerebral artery (MCA). VTX (10 mg/kg/day) was administered orally for14 days prior to the onset of the middle cerebral artery occlusion (MCAO). Behavioral assessments were carried out 24 hours after the MCAO technique.The hippocampal and cortical tissues of the brain were isolated to assess the histological changes and the levels of the biochemical parameters.Damage from MCAO resulted in significant neurological impairments as well as histopathological damage. VTX, on the other hand, alleviated MCAO-induced neurological impairments and histological abnormalities in both hippocampus and cortical tissues of ischemic rats. Western blot analysis indicated significant rises of p-PERK, CHOP, ASK-1, NICD, HES-1, HES-5, and p-eIF2Ü expression levels in MCAO rats. Moreover, ELISA revealed an increase in the levels of ATF4, IRE1, Apaf-1, and HIF-1Ü, while VTX administration ameliorated most of these perturbations induced after MCAO injury. This research suggests that VTX could be a potent neuroprotective agent against ischemic stroke by inhibiting a variety of oxidative, apoptotic, inflammatory, and endoplasmic reticulum stress pathways

Issued also as CD