Project/Area Number |
18591218
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Embryonic/Neonatal medicine
|
Research Institution | Osaka University |
Principal Investigator |
WADA Kazuko Osaka University, Faculty of medicine, assistant professor (30294094)
|
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)
田村 有広 大阪大学, 医学部附属病院, 医員(研究職) (50379187)
|
Project Period (FY) |
2006 – 2007
|
Project Status |
Completed (Fiscal Year 2007)
|
Budget Amount *help |
¥3,930,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥330,000)
Fiscal Year 2007: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2006: ¥2,500,000 (Direct Cost: ¥2,500,000)
|
Keywords | hypoxic-ischemic injury / prostaglandin D2 / brain edema |
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.
|