title: Ulinastatin downregulates TLR4 and NF-kB expression and protects mouse brains against ischemia/reperfusion injury.
abstract: BACKGROUND
  Inflammatory damage plays an important role in ischemic stroke and provides potential targets for therapy. Ulinastatin (UTI), a drug used to treat shock and acute pancreatitis in clinic, has attracted attention for its protective effects through immunomodulatory and anti-inflammatory properties. However, the effect of UTI in the acute phase of cerebral ischemia/reperfusion (I/R) is not clear. This study is to investigate the potential neuroprotective effect of UTI and explore its underlying mechanisms.
  
  
  METHODS
  Male CD-1 mice were subjected to transient middle cerebral artery occlusion (tMCAO) and randomly assigned into four groups: Sham (sham-operated) group, tMCAO (tMCAO + 0.9% saline) group, UTI-L (tMCAO + UTI 1500 U/100 g), and UTI-H (tMCAO + UTI 3000 U/100 g) group. UTI was administered immediately after reperfusion in the UTI-L and UTI-H groups. About 24 h after the reperfusion, the neurological deficit, brain water content, and infarct volume were detected. Immunohistochemistry, western blot and quantitative reverse transcription polymerase chain reaction (qRT-PCR) were used to detect the expression of TLR4 and NF-κB in the ischemic cerebral cortex.
  
  
  RESULTS
  Compared with tMCAO group, both UTI-L and UTI-H groups dramatically ameliorated neurological deficit (p < 0.05), lessened the brain water content (p < 0.05) and infarct volume (p < 0.05), and decreased the expression of TLR4 and NF-κB.
  
  
  CONCLUSIONS
  These results showed that UTI protected the brain against ischemic injury which may be due to the alleviation of inflammation reaction in early stage through downregulating TLR4 and NF-κB expression.
authors.affiliation: a Department of Neurology , Affiliated Hospital of Hebei University , Baoding , PR China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Li
authors.affiliation: a Department of Neurology , Affiliated Hospital of Hebei University , Baoding , PR China.
authors.forename: Likai
authors.initials: L
authors.lastname: Su
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Xiangjian
authors.initials: X
authors.lastname: Zhang
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Zhang
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Lina
authors.initials: L
authors.lastname: Wang
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Yaoru
authors.initials: Y
authors.lastname: Li
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Tingting
authors.initials: T
authors.lastname: He
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Xingyuan
authors.initials: X
authors.lastname: Zhu
authors.affiliation: b Department of Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , China.|c Hebei Key Laboratory for Neurology , Second Hospital of Hebei Medical University , Shijiazhuang , PR China.
authors.forename: Lili
authors.initials: L
authors.lastname: Cui
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects; D004353:Drug Evaluation, Preclinical; D006023:Glycoproteins / Q000494:pharmacology*; D020244:Infarction, Middle Cerebral Artery / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D011897:Random Allocation; D015427:Reperfusion Injury / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051197:Toll-Like Receptor 4 / Q000378:metabolism*
chemical_list: D006023:Glycoproteins; D016328:NF-kappa B; D018696:Neuroprotective Agents; D012333:RNA, Messenger; C493487:Tlr4 protein, mouse; D051197:Toll-Like Receptor 4; C028665:urinastatin
keywords: Cerebral ischemia/reperfusion; inflammatory; nuclear factor-kappa B; toll-like receptor 4; ulinastatin