Synthesis of Compounds with Properties of Leukotrienes C ₄ and D ₄ in Gerbil Brains After Ischemia and Reperfusion

Abstract

6-Sulfidopeptide-containing leukotriene-like immunoreactivity was synthesized in gerbil forebrains after bilateral common carotid occlusion and reperfusion. At 5, 10, or 15 minutes of ischemia, concentrations increased significantly and became more marked on reperfusion. Immunoreactivity was highest in forebrain gray matter and was below the detection limit of the assay in brain regions remote from the zone of ischemia. In vitro experiments with vascular cells and organ cultures of cerebral arteries indicate that the cerebral blood vessel wall is not a major source of biosynthetic activity in the brain. These experiments demonstrate leukotriene biosynthesis by the brain. Because synthesis occurs during ischemia and reperfusion and because leukotrienes are potent vasoconstrictors and promoters of tissue edema, they may play a role in the pathophysiology of cerebral ischemia.

Identification and quantitative analysis of hydroxy-eicosatetraenoic acids in rat brains exposed to regional ischemia.

“…The increased synthesis of leukotrienes C 4 and D 4 in the gerbil forebrain following ischemia and reperfusion may indicate the involvement of leukotrienes in the mechanism of ischemic edema formation. 22 Our study did not aim at detecting leukotrienes, but the presence of 5-HETE in the ischemic rat brain disclosed by this study suggests the involvement of leukotrienes in the same area because 5-HETE and leukotrienes are derived from the same precursor, 5-HPETE.…”

Cerebral Blood Flow and O2 Metabolism after Asphyxia in Neonatal Lambs

“…The lipoxygenase pathway of arachidonate metabolism is also important to consider in this regard. Leukotrienes are cerebral vasoconstrictors (41) and their production has also been shown to be increased during recirculation after cerebral ischemia (42). CMR0 2 is also depressed during the late period after asphyxia.…”

Leukotriene Signaling in Atherosclerosis and Ischemia

“…The notion of LT production in the ischemic brain was firstly raised by studies in gerbils [71], in which inhibitors of LT synthesis limit the damage after transient cerebral ischemia [72]. Subsequent studies in rats have associated beneficial effects with the cysteinyl-LT arm of the AA metabolism.…”