en Protective Effect of Ipragliflozin on Acute Brain Injury Induced by Endotoxemia in Mice Aims: This study was done to investigate the potential neuroprotective effect of ipragliflozin during endotoxemia in mice. Materials & Methods: Twenty-four adult male Swiss-albino mice aged 8-12 weeks (25-35g) were randomized into four equal groups (n=6): sham (laparotomy without cecal ligation and puncture (CLP), sepsis (laparotomy with CLP), vehicle (equivalent volume of DMSO before CLP), and ipragliflozin (3mg/kg/day, orally before CLP). Tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), IL-1β, toll-like receptor 4 (TLR4), and P-signal transducer and activator of transcription (STAT)-3 levels were assessed in the brain tissue and histological examination was done. Findings: The tissue levels of TNF-α, IL-6, and IL-1B in the sham group were much lower than in the sepsis and vehicle groups. Furthermore, the ipragliflozin group had considerably lower tissue levels of TNF-α, IL-6, and IL-1B compared to the sepsis and vehicle groups. However, the sham group showed much lower tissue levels of TLR4 and STAT3 compared to the sepsis and vehicle groups. Also, the tissue levels of TLR4 and STAT3 in the ipragliflozin group were considerably lower than those in the sepsis and vehicle groups. Histopathology analysis demonstrated that ipragliflozin might considerably reduce brain damage compared to sepsis and vehicle groups that showed interstitial edema and included glial cells with pyknotic nuclei. Conclusion: Ipragliflozin attenuates brain dysfunction during CLP-induced polymicrobial sepsis in male mice.   Endotoxemia,Sepsis,Tumor necrosis factor-alpha,Toll-like receptor 4, 225 231 http://ijwph.ir/browse.php?a_code=A-10-1857-9&slc_lang=en&sid=3 A.R. Mohammad 1003194753284600378895 1003194753284600378895 No Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq A.A. Shnaien ealkhazaaly@gmail.com 1003194753284600378894 1003194753284600378894 No Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq S.K. Alabsawy 1003194753284600378893 1003194753284600378893 No Department of Physiology & Pharmacology, Faculty of Veterinary Medicine, University of Kufa, Najaf, Iraq E.S. Hassan 1003194753284600378892 1003194753284600378892 Yes Department of Pharmacology & Therapeutics, Faculty of Medicine, University of Kufa, Najaf, Iraq