title: The effect of osteopontin and osteopontin-derived peptides on preterm brain injury.
abstract: BACKGROUND
  Osteopontin (OPN) is a highly phosphorylated sialoprotein and a soluble cytokine that is widely expressed in a variety of tissues, including the brain. OPN and OPN-derived peptides have been suggested to have potential neuroprotective effects against ischemic brain injury, but their role in preterm brain injury is unknown.
  
  
  METHODS
  We used a hypoxia-ischemia (HI)-induced preterm brain injury model in postnatal day 5 mice. OPN and OPN-derived peptides were given intracerebroventricularly and intranasally before HI. Brain injury was evaluated at 7 days after the insults.
  
  
  RESULTS
  There was a significant increase in endogenous OPN mRNA and OPN protein in the mouse brain after the induction of HI at postnatal day 5. Administration of full-length OPN protein and thrombin-cleaved OPN did not affect preterm brain injury. This was demonstrated with both intracerebroventricular and intranasal administration of OPN as well as in OPN-deficient mice. Interestingly, both N134-153 and C154-198 OPN-derived peptides increased the severity of brain injury in this HI-induced preterm brain injury model.
  
  
  CONCLUSIONS
  The neuroprotective effects of OPN are age-dependent, and, in contrast to the more mature brain, OPN-derived peptides potentiate injury in postnatal day 5 mice. Intranasal administration is an efficient way of delivering drugs to the central nervous system (CNS) in neonatal mice and is likely to be an easy and noninvasive method of drug delivery to the CNS in preterm infants.
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. anna-maj.albertsson@neuro.gu.se.
authors.forename: Anna-Maj
authors.initials: AM
authors.lastname: Albertsson
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. Xiaoli.Zhang@neuro.gu.se.|Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front St, 450052, Zhengzhou, China. Xiaoli.Zhang@neuro.gu.se.
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Cancer, Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA, 02115, USA. Jianmei_Leavenworth@DFCI.HARVARD.EDU.|Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, 02115, USA. Jianmei_Leavenworth@DFCI.HARVARD.EDU.
authors.forename: Jianmei
authors.initials: J
authors.lastname: Leavenworth
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. Dan.Bi@neuro.gu.se.|Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front St, 450052, Zhengzhou, China. Dan.Bi@neuro.gu.se.
authors.forename: Dan
authors.initials: D
authors.lastname: Bi
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. Syam.Nair@neuro.gu.se.
authors.forename: Syam
authors.initials: S
authors.lastname: Nair
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. qiaolili1976@163.com.|Department of Pediatrics, Song Jiang Central Hospital, 746 Songjiang Zhongshan West Rd, 201600, Shanghai, China. qiaolili1976@163.com.
authors.forename: Lili
authors.initials: L
authors.lastname: Qiao
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. henrik.hagberg@obgyn.gu.se.|Perinatal Center, Department of Obstetrics and Gynecology, Sahlgrenska Academy at University of Gothenburg, Journalvägen 6, 41685, Gothenburg, Sweden. henrik.hagberg@obgyn.gu.se.|Department of Perinatal Imaging and Health, Division of Imaging Sciences and Biomedical Engineering, King's College London, King's Health Partners, St. Thomas' Hospital, London, SE1 7EH, UK. henrik.hagberg@obgyn.gu.se.
authors.forename: Henrik
authors.initials: H
authors.lastname: Hagberg
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. carina.mallard@neuro.gu.se.
authors.forename: Carina
authors.initials: C
authors.lastname: Mallard
authors.affiliation: Department of Cancer, Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, 1 Jimmy Fund Way, Boston, MA, 02115, USA. harvey_cantor@dfci.harvard.edu.|Department of Microbiology and Immunobiology, Division of Immunology, Harvard Medical School, 77 Ave Louis Pasteur, Boston, MA, 02115, USA. harvey_cantor@dfci.harvard.edu.
authors.forename: Harvey
authors.initials: H
authors.lastname: Cantor
authors.affiliation: Perinatal Center, Department of Neuroscience and Physiology, Sahlgrenska Academy at University of Gothenburg, Box 432, SE-405 30, Gothenburg, Sweden. xiaoyang.wang@fysiologi.gu.se.|Department of Pediatrics, The Third Affiliated Hospital of Zhengzhou University, 7 Kangfu Front St, 450052, Zhengzhou, China. xiaoyang.wang@fysiologi.gu.se.
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Wang
mesh_terms: D000281:Administration, Intranasal; D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001930:Brain Injuries / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D005260:Female; D007276:Injections, Intraventricular; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D053495:Osteopontin / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000235:genetics; D010446:Peptide Fragments / Q000008:administration & dosage* / Q000096:biosynthesis* / Q000235:genetics; D016896:Treatment Outcome
chemical_list: D010446:Peptide Fragments; D053495:Osteopontin