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We investigated the role of PGD<jats:sub>2<\/jats:sub>in the pathogenesis of hypoxic-ischemic encephalopathy (HIE) in neonatal mice at postnatal day 7. In wild-type mice, hypoxia-ischemia increased PGD<jats:sub>2<\/jats:sub>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<jats:italic>L-PGDS<\/jats:italic>or<jats:italic>DP<\/jats:italic><jats:sub>2<\/jats:sub>knock-out mouse brains compared with that in the wild-type HIE brains, it was significantly increased in<jats:italic>HPGDS\u2013L-PGDS<\/jats:italic>double knock-out or<jats:italic>DP<\/jats:italic><jats:sub>1<\/jats:sub>knock-out mice. The PGD<jats:sub>2<\/jats:sub>level in<jats:italic>L-PGDS<\/jats:italic>,<jats:italic>HPGDS<\/jats:italic>, and<jats:italic>HPGDS\u2013L-PGDS<\/jats:italic>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 PGD<jats:sub>2<\/jats:sub>production. DP<jats:sub>1<\/jats:sub>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<jats:italic>HPGDS\u2013L-PGDS<\/jats:italic>knock-out mice. Endothelial cells were severely damaged in<jats:italic>HPGDS\u2013L-PGDS<\/jats:italic>and<jats:italic>DP<\/jats:italic><jats:sub>1<\/jats:sub>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 PGD<jats:sub>2<\/jats:sub>protected the neonatal brain from hypoxic-ischemic injury mainly via DP<jats:sub>1<\/jats:sub>receptors by preventing endothelial cell degeneration.<\/jats:p>","DOI":"10.1523\/jneurosci.0321-07.2007","type":"journal-article","created":{"date-parts":[[2007,4,18]],"date-time":"2007-04-18T16:48:03Z","timestamp":1176914883000},"page":"4303-4312","source":"Crossref","is-referenced-by-count":74,"title":["Prostaglandin D<sub>2<\/sub>Protects Neonatal Mouse Brain from Hypoxic Ischemic Injury"],"prefix":"10.1523","volume":"27","author":[{"given":"Hidetoshi","family":"Taniguchi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ikuko","family":"Mohri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hitomi","family":"Okabe-Arahori","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kosuke","family":"Aritake","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuko","family":"Wada","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahisa","family":"Kanekiyo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shuh","family":"Narumiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiro","family":"Nakayama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keiichi","family":"Ozono","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Urade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masako","family":"Taniike","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"393","published-online":{"date-parts":[[2007,4,18]]},"reference":[{"key":"2023041303245864000_27.16.4303.1","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000060204.67672.8B"},{"key":"2023041303245864000_27.16.4303.2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1748-1716.1991.tb09204.x"},{"key":"2023041303245864000_27.16.4303.3","unstructured":"American College of Obstetricians and Gynecologists, American Academy of Pediatrics (2003) Neonatal encephalopathy and cerebral palsy: defining the pathogenesis and pathophysiology (American College of Obstetricians and Gynecologists, Washington, DC)."},{"key":"2023041303245864000_27.16.4303.4","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410410416"},{"key":"2023041303245864000_27.16.4303.5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.2.726"},{"key":"2023041303245864000_27.16.4303.6","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000138023.60272.9e"},{"key":"2023041303245864000_27.16.4303.7","doi-asserted-by":"publisher","DOI":"10.1038\/nm0603-669"},{"key":"2023041303245864000_27.16.4303.8","doi-asserted-by":"publisher","DOI":"10.1016\/S0095-5108(02)00059-3"},{"key":"2023041303245864000_27.16.4303.9","doi-asserted-by":"crossref","unstructured":"Gustavsson M Mallard C Vannucci SJ Wilson MA Johnston MV Hagberg H (2007) Vascular response to hypoxic preconditioning in the immature brain. 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