title: Effects of recombinant osteopontin on blood-brain barrier disruption after subarachnoid hemorrhage in rats.
abstract: OBJECTIVE
  We determined effects of recombinant OPN (r-OPN), a pleiotropic extracellular matrix protein, on blood-brain barrier (BBB) disruption and matrix metalloproteinase (MMP)-9 activation after subarachnoid hemorrhage (SAH) in rats.
  
  
  METHODS
  The endovascular perforation model of SAH was used. SAH or sham-operated rats were treated with pre-SAH intracerebroventricular administration of two dosages of r-OPN, r-OPN+GRGDSP (an L-arginyl-glycyl-L-aspartate-dependent integrin receptor antagonist), albumin or vehicle. Neurological impairments, brain edema and BBB disruption were evaluated, and Western blot analyses were performed in the brain at 24 h after SAH.
  
  
  RESULTS
  r-OPN significantly prevented brain edema and BBB disruption compared with the control rats, associated with the suppression of nuclear factor-κB and mitogen-activated protein kinase pathways, leading to MMP-9 inactivation. These effects were blocked by GRGDSP.
  
  
  CONCLUSIONS
  L-arginyl-glycyl-L-aspartate-dependent integrin receptor-mediated multiple signaling pathways may be involved in the protective effects of r-OPN against BBB disruption after SAH.
authors: Department of Physiology, Loma Linda University, School of Medicine, Loma Linda, CA 92354, USA.
authors: Hidenori
authors: H
authors: Suzuki
authors: Yu
authors: Y
authors: Hasegawa
authors: Robert
authors: R
authors: Ayer
authors: Takashi
authors: T
authors: Sugawara
authors: Wanqiu
authors: W
authors: Chen
authors: Takumi
authors: T
authors: Sozen
authors: Kenji
authors: K
authors: Kanamaru
authors: Waro
authors: W
authors: Taki
authors: John H
authors: JH
authors: Zhang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000503:physiopathology*; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D016009:Chi-Square Distribution; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005786:Gene Expression Regulation / Q000187:drug effects; D051550:I-kappa B Kinase / Q000378:metabolism; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009422:Nervous System Diseases / Q000188:drug therapy / Q000209:etiology; D009460:Neurologic Examination; D009842:Oligopeptides / Q000627:therapeutic use; D053495:Osteopontin / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000627:therapeutic use; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000188:drug therapy / Q000473:pathology*
chemical_list: D009842:Oligopeptides; D011994:Recombinant Proteins; D053495:Osteopontin; C058161:glycyl-arginyl-glycyl-aspartyl-seryl-proline; D051550:I-kappa B Kinase; D048670:MAP Kinase Kinase 4; D020780:Matrix Metalloproteinase 9