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The effect of prostaglandin D2 in neonatal hypoxic-ischemic injury

Research Project

Project/Area Number 18591218
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Embryonic/Neonatal medicine
Research InstitutionOsaka University

Principal Investigator

WADA Kazuko  Osaka University, Faculty of medicine, assistant professor (30294094)

Co-Investigator(Kenkyū-buntansha) TANIIKE Masako  Osaka Univetsty, Faculty of medicine, Specially Appointed Professor (30263289)
ARAHORI Hitomi  Osaka Univetsty, Faculty of medicine, assistant professor (40379186)
田村 有広  大阪大学, 医学部附属病院, 医員(研究職) (50379187)
Project Period (FY) 2006 – 2007
Project Status Completed (Fiscal Year 2007)
Budget Amount *help
¥3,930,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
Keywordshypoxic-ischemic injury / prostaglandin D2 / brain edema
Research Abstract

Prostaglandin D2 (PGD) is synthesized by hematopoietic PGD synthase (HPGDS) or lipocalin-type PGDS (L-PGDS), depending on the organ in which it is produced, and binds specifically to either DP1 or DP2 receptors. We investigated the role of PGD2 in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonatal mice at postnatal day 7. In wild-type mice, hypoxia-ischemia increased PGD2 production in the brain up to 90-fold compared with the level in sham-operated brains at 10 min after cessation of hypoxia. Whereas the size of the infarct was not changed in L-PGDS or DP2 knock-out mouse brains compared with that in the wild-type HIE brains, it was significantly increased in HPGDS-L-PGDS double knock-out or DP1 knock-out mice. The PGD2 level in L-PGDS, HPGDS, and HPGDS-L-PGDS knock-out mice at 10 min of reoxygenation was 46, 7, and 1%, respectively, of that in the wild-type ones, indicating the infarct size to be in inverse relation to the amount of PGD2 production. DP1 receptors were exclusively expressed in endothelial cells after 1 h of reoxygenation, and cerebral blood flow decreased more rapidly after the onset of hypoxia and did not return to the baseline level after reoxygenation in HPGDS-L-PGDS knock-out mice. Endothelial cells were severely damaged in HPGDS-L-PGDS and DP1 knock-out mice after 1 h of reoxygenation. In the human neonatal HIE brain, HPGDS-positive microglia were increased in number. In conclusion, it is probable that PGD2 protected the neonatal brain from hypoxic-ischemic injury mainly via DPI receptors by preventing endothelial cell degeneration.

Report

(3 results)
  • 2007 Annual Research Report   Final Research Report Summary
  • 2006 Annual Research Report
  • Research Products

    (16 results)

All 2007 2006

All Journal Article (16 results) (of which Peer Reviewed: 7 results)

  • [Journal Article] Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains.2007

    • Author(s)
      Taniguchi H, Okabe-Arahori H, Wada K, et. al.
    • Journal Title

      Neurosci Lett. 420(1)

      Pages: 39-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic in jury.2007

    • Author(s)
      Taniguchi H, Okabe-Arahori H, Wada K, et. al.
    • Journal Title

      J Neurosci. 27(16)

      Pages: 4303-12

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Sonographic femur length to trunk cross area ratio: prediction of fetal outcome in 30 cases in which micromelia was suspected.2007

    • Author(s)
      Arahori H, Tamura A, Wasada K, Shimoya K, Wada K, Murata Y, Ozono K.
    • Journal Title

      J Obstet Gynaecol Res. 33(3)

      Pages: 284-53

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Hematopoietic prostaglandin D synthase and DPl receptor are selectively upregulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer disease.2007

    • Author(s)
      Mohri I, Urade Y, Taniike M, et. al.
    • Journal Title

      J Neuropathol Exp Neurol. 66(6).

      Pages: 469-80

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid.2007

    • Author(s)
      Kanekiyo T, Ozono K, Taniike M, et. al.
    • Journal Title

      Proc Natl Acad Sci U S A. 10;104(15)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2007 Annual Research Report 2007 Final Research Report Summary
    • Peer Reviewed
  • [Journal Article] Early induction of neuronal lipocalin-type prostaglandin D synthase after hypoxic-ischemic injury in developing brains2007

    • Author(s)
      Taniguchi, H, Okabe-Arahori, H, Wada, K, et. al.
    • Journal Title

      Neurosci lett 420(1)

      Pages: 39-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury2007

    • Author(s)
      Taniguchi, H, Okabe-Arahori, H, Wada, K, et. al.
    • Journal Title

      J Neurosci 27(16)

      Pages: 4308-12

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Sonographic femur length to trunk cross area ratio : prediction of fetal outcome in 30 cases in which micromelia was suspected2007

    • Author(s)
      Arahori, H, Tamura, A, Wasada, K, Shimoya, K, Wada, K, Murata, Y, Ozono, K
    • Journal Title

      J Obstet Gynaecol Res 33(3)

      Pages: 284-53

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Hematopoietic prostaglandin D synthase and DPI receptor are selectively unregulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer disease2007

    • Author(s)
      Mohri, I, Urade, Y, Taniike, M, et. al.
    • Journal Title

      J Neuropathol Exp Nerol 66(6)

      Pages: 469-80

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Lipocalin-type prostaglandin D synthase/beta-trace is a major amyloid beta-chaperone in human cerebrospinal fluid2007

    • Author(s)
      Kanekiyo, T, Ozono, K, Taniike, M, et. al.
    • Journal Title

      Proc Nati Acad Sci USA 10 104(15)

      Pages: 6412-7

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2007 Final Research Report Summary
  • [Journal Article] Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury.2007

    • Author(s)
      Taniguchi H, Okabe-Arahori H, Wada K, et. al.
    • Journal Title

      J neurosci. 27(16)

      Pages: 4303-12

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Hematopoietic prostaglandin D synthase and DP1 receptor are selectively upregulated in microglia and astrocytes within senile plaques from human patients and in a mouse model of Alzheimer disease.2007

    • Author(s)
      Mohri I, Urade Y, Taniike M, et. al.
    • Journal Title

      J Neuropathol Exp Neurol. 66(6).

      Pages: 469-80

    • Related Report
      2007 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Prostaglandin D2-mediated microglia/astrocyte interaction enhances astrogliosis and demyelination in twitcher.2006

    • Author(s)
      Mohri I, Taniike M, Taniguchi H, et al.
    • Journal Title

      J.Neurosci. 19;26(16)

      Pages: 4383-4393

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Six novel mutations detected in the GALC gene in 17 Japanese patients with Krabbe disease, and new genotype-phenotype correlation.2006

    • Author(s)
      Xu C, Sakai N, Taniike M, Inui K, Ozono K
    • Journal Title

      J Hum Gent. 51(6)

      Pages: 548-554

    • NAID

      10017608409

    • Related Report
      2006 Annual Research Report
  • [Journal Article] Lipocalin-type prostaglandin D synthase is up-regulated in oligodendrocytes in lysosomal storage diseases and binds gangliosides.2006

    • Author(s)
      Mohri I, Taniike M, Okazaki I, et al.
    • Journal Title

      J Neurochem. 97(3)

      Pages: 641-651

    • Related Report
      2006 Annual Research Report
  • [Journal Article] CMV DNA detection in dried blood spots for diagnosing congenital CMV infection in Japan.2006

    • Author(s)
      Yamagishi Y, Wada K, Arahori H, Tamura A, et al.
    • Journal Title

      J Med Virol. 78(7)

      Pages: 923-925

    • Related Report
      2006 Annual Research Report

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Published: 2006-04-01   Modified: 2016-04-21  

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