title: Osteopontin reduced hypoxia-ischemia neonatal brain injury by suppression of apoptosis in a rat pup model.
abstract: OBJECTIVE
  Osteopontin (OPN) is neuroprotective in ischemic brain injuries in adult experimental models; therefore, we hypothesized that OPN would provide neuroprotection and improve long-term neurological function in the immature brain after hypoxic-ischemic (HI) injury.
  
  
  METHODS
  HI was induced by unilateral ligation of the right carotid artery followed by hypoxia (8% O(2) for 2 hours) in postnatal Day 7 rats. OPN (0.03 μg or 0.1 μg) was injected intracerebroventricularly at 1 hour post-HI. Temporal expression of endogenous OPN was evaluated in the normal rat brain at the age of 0, 4, 7, 11, 14, and 21 days and in the ipsilateral hemisphere after HI. The effects of OPN were evaluated using 2-3-5-triphenyl tetrazolium chloride staining, apoptotic cell death assay, and cleaved caspase-3 expression. Neurological function was assessed by the Morris water maze test.
  
  
  RESULTS
  Endogenous OPN expression in the brain was the highest at the age of 0 day with continuous reduction until the age of 21 days during development. After HI injury, endogenous OPN expression was increased and peaked at 48 hours. Exogenous OPN decreased infarct volume and improved neurological outcomes 7 weeks after HI injury. OPN-induced neuroprotection was blocked by an integrin antagonist.
  
  
  CONCLUSIONS
  OPN-induced neuroprotection was associated with cleaved-caspase-3 inhibition and antiapoptotic cell death. OPN treatment improved long-term neurological function against neonatal HI brain injury.
authors.affiliation: Department of Physiology and Pharmacology, Loma Linda University School of Medicine, Risley Hall, Room 214, Loma Linda, CA 92350, USA.
authors.forename: Wanqiu
authors.initials: W
authors.lastname: Chen
authors.forename: Qingyi
authors.initials: Q
authors.lastname: Ma
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.forename: Richard
authors.initials: R
authors.lastname: Hartman
authors.forename: Jiping
authors.initials: J
authors.lastname: Tang
authors.forename: John H
authors.initials: JH
authors.lastname: Zhang
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D017209:Apoptosis / Q000502:physiology*; D051017:Apoptosis Regulatory Proteins / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use; D053148:Caspase 3 / Q000378:metabolism / Q000502:physiology; D061945:Caspase Inhibitors; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D004195:Disease Models, Animal; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology* / Q000517:prevention & control*; D053495:Osteopontin / Q000008:administration & dosage / Q000502:physiology* / Q000627:therapeutic use; D051381:Rats
chemical_list: D051017:Apoptosis Regulatory Proteins; D061945:Caspase Inhibitors; D053495:Osteopontin; D053148:Caspase 3