Arachidonic Acid Induces Opening of the Blood-Brain Barrier

Abstract

A broad spectrum of cerebral insults causes a liberation of arachidonic acid in brain tissue. The membrane-bound arachidonic acid pool decreases markedly during hypoxia and a few minutes after the onset of cerebral ischemia [3, 7]. Moreover, recirculation after ischemia is associated with the appearance of metabolites of arachidonic acid, such as prostaglandins and leukotrienes [11]. Experimentally induced seizures also induce release of free unsaturated fatty acids [2], Moreover, considerable amounts of arachidonic acid were detected in vasogenic edema fluid produced by a cortical freezing lesion [9]. In addition, this compound has been detected in CSF of patients with severe head injuries [10]. Arachidonic acid and its metabolites, prostaglandins, leukotrienes, and free radicals are regarded as potent mediators of secondary brain damage such as cytotoxic and vasogenic brain edema [1]. Exposure of brain slices to arachidonic acid induces cytotoxic cell swelling [5]. Inhibition of Na⁺/K⁺-ATPase and uncoupling of oxidative phosphorylation are thought to be the molecular cytotoxic mechanisms [6], Moreover, arachidonic acid and free radicals were found to produce endothelial lesions, such as “dome-like protrusions” and “craters” in cerebral arterioles when extravascularly applied to pial vessels [8].

The study reported in this paper was supported by a grant from the Deutsche Forschungsgemeinschaft (Ba 452/6–5).