2007 Fiscal Year Final Research Report Summary
The effect of prostaglandin D2 in neonatal hypoxic-ischemic injury
| Project/Area Number |
18591218
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Embryonic/Neonatal medicine
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| Research Institution | Osaka University |
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Principal Investigator |
WADA Kazuko Osaka University, Faculty of medicine, assistant professor (30294094)
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| 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)
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| Project Period (FY) |
2006 – 2007
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| Keywords | hypoxic-ischemic injury / prostaglandin D2 / brain edema |
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| 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.
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[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
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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
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