Prostaglandin endoperoxide synthase-2 abundance is increased in brain tissues of late-gestation fetal sheep in response to cerebral hypoperfusion.
OBJECTIVE
To determine the mechanism by which cerebral hypoperfusion enhances prostanoid secretion by fetal brain tissues.


METHODS
Studies were performed on five intact and five carotid sinus-denervated sheep fetuses (124-136 days) exposed to 10 minutes of cerebral hypoperfusion. Plasma collected from lingual artery and sagittal sinus, and microdialysates collected from brain stem and hypothalamus were assayed for prostanoid production. Fetal hypothalamus, cerebral cortex, hippocampus, cerebellum, and brain stem were collected from intact animals and 30 minutes after cerebral hypoperfusion for the expression, activity, and distribution of prostaglandin endoperoxide synthase-1 (PGHS-1), PGHS-2, and thromboxane synthase.


RESULTS
Thromboxane B2 increased significantly in sagittal sinus compared with arterial blood, but PGE2 did not change. Thromboxane B2 decreased in brain stem and hypothalamus microdialysates, and prostaglandin E2 increased in these regions. PGHS-2 immunoreactive protein levels in brain tissues increased in the cerebral hypoperfusion fetuses compared with those of the intact animals. By contrast, PGHS-1 and thromboxane synthase protein levels did not change between these two groups. Prostaglandin endoperoxide synthase activity in brain tissues decreased with the increased levels of immunoreactive PGHS-2.


CONCLUSIONS
1) Prostanoids are produced in response to cerebral hypoperfusion, 2) the increase in the production of prostanoid responses to cerebral hypoperfusion is associated with the decrease in activity of, and therefore, the "suicide" inactivation of PGHS, and 3) PGHS-2 is the predominant form of PGHS, whose synthesis is induced by cerebral hypoperfusion in the fetal brain.
Tong
H
H
Department of Physiology, University of Florida College of Medicine, Gainesville 32610, USA.
Richards
E
E
Wood
C E
CE
D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology* / Q000378:metabolism; D002545:Brain Ischemia / Q000201:enzymology* / Q000378:metabolism; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D015232:Dinoprostone / Q000096:biosynthesis; D005333:Fetus / Q000201:enzymology / Q000378:metabolism; D005865:Gestational Age; D007527:Isoenzymes / Q000096:biosynthesis / Q000378:metabolism*; D010544:Peroxidases / Q000378:metabolism*; D011451:Prostaglandin-Endoperoxide Synthases / Q000096:biosynthesis / Q000378:metabolism*; D012756:Sheep; D013929:Thromboxane B2 / Q000097:blood; D013930:Thromboxane-A Synthase / Q000096:biosynthesis / Q000378:metabolism; D013997:Time Factors; D014018:Tissue Distribution
D007527:Isoenzymes; D013929:Thromboxane B2; D010544:Peroxidases; D051545:Cyclooxygenase 1; D051546:Cyclooxygenase 2; D011451:Prostaglandin-Endoperoxide Synthases; D013930:Thromboxane-A Synthase; D015232:Dinoprostone