title: Ucf-101 protects against cerebral oxidative injury and cognitive impairment in septic rat.
abstract: BACKGROUND
  Omi/HtrA2 is a proapoptotic mitochondrial serine protease involved in caspase-dependent and caspase-independent cell apoptosis. It has been verified that Omi/HtrA2 is related to apoptosis due to oxidative stress, which may play an important role in the integrity of mitochondria. Ucf-101 is a specific inhibitor of Omi/HtrA2 and it has been demonstrated that Ucf-101 has organ protective effects in a variety of in vitro and in vivo studies. The aim of our study was to examine the neuroprotective effects of Ucf-101 on cerebral oxidative injury and cognitive impairment in septic rats.
  
  
  METHODS
  Male Sprague Dawley rats are subjected to cecal ligation and puncture (CLP) or sham-operated laparotomy. Rats were divided into 4 groups: (1) a sham group plus normal saline (10 mL/kg); (2) a sham group plus Ucf-101 (10 umol/kg); (3) CLP plus normal saline (10 mL/kg); and (4) CLP plus Ucf-101 (10 umol/kg). Brain tumor necrosis factor (TNF)-α level, caspase-3 and caspase-9 activities, malondialdehyde (MDA) content and catalase (CAT) activities were examined. TUNEL staining was utilized to evaluate the amount of apoptosis and the cognitive function was evaluated by the MWM test. The study also assessed the clinical scores of animals and the survival time for the 7-day period.
  
  
  RESULTS
  CLP resulted in a poor survival rate, evidence of hippocampal oxidative injury, cell apoptosis and cognitive dysfunction as well as elevated TNF-α level and caspases activities, increased weight loss and clinical scores. Ucf-101 pre-treatment could significantly inhibit caspases activities and cell apoptosis, reduce TNF-α and MDA levels, slightly reverse CAT activities in the brain and attenuate this CLP effect on cognitive dysfunction. In addition, the survival rate and survival time was significantly improved by pre-treatment with Ucf-101.
  
  
  CONCLUSIONS
  The present results demonstrated that ucf-101 has the neuroprotective effects on cerebral oxidative injury and cognitive impairment in septic rats.
authors.affiliation: Department of Intensive Care Unit, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, China.
authors.forename: YueYu
authors.initials: Y
authors.lastname: Hu
authors.forename: Man
authors.initials: M
authors.lastname: Huang
authors.forename: Pengfei
authors.initials: P
authors.lastname: Wang
authors.forename: Qiuping
authors.initials: Q
authors.lastname: Xu
authors.forename: BaoRong
authors.initials: B
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001927:Brain Diseases / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D003072:Cognition Disorders / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D011744:Pyrimidinones / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D013871:Thiones / Q000494:pharmacology / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018696:Neuroprotective Agents; D011744:Pyrimidinones; D013871:Thiones; D014409:Tumor Necrosis Factor-alpha; C501517:UCF 101; D008315:Malondialdehyde; D053148:Caspase 3; D053453:Caspase 9