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 journalArticle

59 Citations (Scopus)

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
Externally publishedYes

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prostaglandin R2 D-isomerase
Prostaglandin D2
Wounds and Injuries
Brain
Knockout Mice
Brain Hypoxia-Ischemia
Endothelial Cells
Cerebrovascular Circulation

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

Cite this

Taniguchi, H., Mohri, I., Okabe-Arahori, H., Aritake, K., Wada, K., Kanekiyo, T., ... Taniike, M. (2007). Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury. Journal of Neuroscience, 27(16), 4303-4312. https://doi.org/10.1523/JNEUROSCI.0321-07.2007

Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury. / Taniguchi, Hidetoshi; Mohri, Ikuko; Okabe-Arahori, Hitomi; Aritake, Kosuke; Wada, Kazuko; Kanekiyo, Takahisa; Narumiya, Shuh; Nakayama, Masahiro; Ozono, Keiichi; Urade, Yoshihiro; Taniike, Masako.

In: Journal of Neuroscience, Vol. 27, No. 16, 18.04.2007, p. 4303-4312.

Research output: Contribution to journalArticle

Taniguchi, H, Mohri, I, Okabe-Arahori, H, Aritake, K, Wada, K, Kanekiyo, T, Narumiya, S, Nakayama, M, Ozono, K, Urade, Y & Taniike, M 2007, 'Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury', Journal of Neuroscience, vol. 27, no. 16, pp. 4303-4312. https://doi.org/10.1523/JNEUROSCI.0321-07.2007
Taniguchi, Hidetoshi ; Mohri, Ikuko ; Okabe-Arahori, Hitomi ; Aritake, Kosuke ; Wada, Kazuko ; Kanekiyo, Takahisa ; Narumiya, Shuh ; Nakayama, Masahiro ; Ozono, Keiichi ; Urade, Yoshihiro ; Taniike, Masako. / Prostaglandin D2 protects neonatal mouse brain from hypoxic ischemic injury. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 16. pp. 4303-4312.
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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.",
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