Effects of Hypoxia and Anoxia on the Ex Vivo Release of Prostaglandins from Mouse Cortical Slices

Abstract: Arachidonic acid is transiently accumulated in the brain as a result of a variety of pathological conditions. The synthesis and release of some of its metabolites, namely, prostaglandin E₂ (PGE₂), thromboxane B₂ (TXB₂), and 6‐keto‐prostaglandin F_1α (6‐keto‐PGF_1α) from cortical slices of mice were studied following exposure to 6 min of hypoxia (7% O₂), 45 s of anoxia, and 5 min‐4 h of reoxygenation following anoxia. Hypoxia induced a slight increase in the rate of TXB₂ release and a slight decrease in the rate of PGE₂ release, whereas 6‐keto‐PGF_1α was unaffected. Anoxia (45 s) followed by reoxygenation induced a transient increase in the release of PGE₂ and of 6‐keto‐PGF_1α with a return to the normal rate at 30 min and 2 h of recovery, respectively. However, the rate of TXB₂ synthesis and release reached its peak (twofold increase) after I h and remained significantly higher than the control rate even after 4 h of normal air breathing. Our results demonstrate that hypoxia and anoxia, even of short duration, selectively trigger the activity of thromboxane synthetase and that this elevated rate of synthesis and release persists long after normal oxygen supply is restored. We suggest that enhanced thromboxane synthesis, with normal prostacyclin levels, might have a role in the pathophysiology of ischemic cell damage.