title: Recombinant osteopontin attenuates brain injury after intracerebral hemorrhage in mice.
abstract: BACKGROUND
  Osteopontin (OPN), an extracellular matrix glycoprotein, has been reported to inhibit inducible nitric oxide synthase (iNOS). We examined if recombinant OPN (r-OPN) inhibits iNOS and prevents brain injury in a mouse collagenase-induced intracerebral hemorrhage (ICH) model.
  
  
  METHODS
  One hundred one mice were randomly assigned to five groups: sham, ICH + vehicle, ICH + r-OPN (10, 50, or 100 ng per mouse) groups. Vehicle or r-OPN was administered via an intracerebroventricular infusion 20 min pre-ICH. Neurological scores and brain water content were evaluated at 24 and 72 h, and hemoglobin assay, Nissl staining and Western blot for iNOS, Stat1, matrix metalloproteinase (MMP)-9 and zonula occludens (ZO)-1 were performed at 24 h post-ICH.
  
  
  RESULTS
  r-OPN did not affect hematoma formation. Middle (50 ng)- and high (100 ng)-dose, but not low (10 ng)-dose of r-OPN treatment significantly improved neurological scores and brain water content compared with the vehicle group. The protective effect of r-OPN was associated with significantly rescued neuronal cells in the peri-hematoma region as well as a decrease in the Stat1 phosphorylation, iNOS induction, MMP-9 activation, and ZO-1 degradation.
  
  
  CONCLUSIONS
  This study suggests that r-OPN may down-regulate iNOS expression by the inhibition of Stat1 phosphorylation, and therefore suppressing the MMP-9 activation, preventing ICH-induced brain injury in mice.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University, Loma Linda, CA 92350, USA.
authors.forename: Bihua
authors.initials: B
authors.lastname: Wu
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Ma
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Chunhua
authors.initials: C
authors.lastname: Chen
authors.forename: Wenwu
authors.initials: W
authors.lastname: Liu
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.forename: John
authors.initials: J
authors.lastname: Zhang
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001929:Brain Edema / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D017364:Collagenases / Q000633:toxicity; D004195:Disease Models, Animal; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D018632:Mice, Inbred SENCAR; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors / Q000378:metabolism; D053495:Osteopontin / Q000494:pharmacology*; D010750:Phosphoproteins / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D050794:STAT1 Transcription Factor / Q000378:metabolism; D014867:Water / Q000378:metabolism; D062826:Zonula Occludens-1 Protein
chemical_list: D008565:Membrane Proteins; D010750:Phosphoproteins; D011994:Recombinant Proteins; D050794:STAT1 Transcription Factor; C494080:Stat1 protein, mouse; C569043:Tjp1 protein, mouse; D062826:Zonula Occludens-1 Protein; D014867:Water; D053495:Osteopontin; D052247:Nitric Oxide Synthase Type II; C496317:Nos2 protein, mouse; D017364:Collagenases; D020780:Matrix Metalloproteinase 9