Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury

Hidetoshi Taniguchi, Ikuko Mohri, Hitomi Okabe-Arahori, Kosuke Aritake, Kazuko Wada, Takahisa Kanekiyo, Shuh Narumiya, Masahiro Nakayama, Keiichi Ozono, Yoshihiro Urade, Masako Taniike

Research output: Contribution to journalArticlepeer-review

61 Scopus citations

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 DP 2 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 DP 1 receptors by preventing endothelial cell degeneration.

Original languageEnglish (US)
Pages (from-to)4303-4312
Number of pages10
JournalJournal of Neuroscience
Volume27
Issue number16
DOIs
StatePublished - Apr 18 2007

Keywords

  • DP receptor
  • Hematopoietic PGD synthase
  • Hypoxic-ischemic encephalopathy
  • Lipocalin-type PGD synthase
  • Microangiopathy
  • Prostaglandin D

ASJC Scopus subject areas

  • Neuroscience(all)

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