Prostaglandin D2Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury
Open Access
- 18 April 2007
- journal article
- Published by Society for Neuroscience in Journal of Neuroscience
- Vol. 27 (16), 4303-4312
- https://doi.org/10.1523/jneurosci.0321-07.2007
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 DP1or DP2receptors. We investigated the role of PGD2in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonatal mice at postnatal day 7. In wild-type mice, hypoxia-ischemia increased PGD2production 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 inL-PGDSorDP2knock-out mouse brains compared with that in the wild-type HIE brains, it was significantly increased inHPGDS–L-PGDSdouble knock-out orDP1knock-out mice. The PGD2level inL-PGDS,HPGDS, andHPGDS–L-PGDSknock-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 PGD2production. DP1receptors 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 inHPGDS–L-PGDSknock-out mice. Endothelial cells were severely damaged inHPGDS–L-PGDSandDP1knock-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 PGD2protected the neonatal brain from hypoxic-ischemic injury mainly via DP1receptors by preventing endothelial cell degeneration.Keywords
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