Eicosanoids in the central nervous system

Abstract

All mammalian tissue investigated to date is capable of eicosanoid biosynthesis in response to various activating stimuli. While the importance of these metabolites as major mediators of many normal physiological processes and some pathophysiological conditions has not been proven, it is evident that these compounds are at least important modulators of many cellular and organ system functions. This review is intended to provide the reader with a brief overview of eicosanoid biology, with specific reference to the neurosciences. The increasing knowledge about the role of the eicosanoids in neurobiology may contribute to the understanding and treatment of many neurological diseases. The eicosanoids comprise several groups of biologically active unsaturated fatty acids: the "primary" prostaglandins, the cyclic endoperoxides, the prostanoids, the leukotrienes, and other acid lipids. This article includes a review of the enzymatic pathways of biosynthesis and metabolism of eicosanoids in man, and the pertinent structural nomenclature. The general basic and clinical pharmacological effects of the more important compounds on vascular perfusion, platelet function, intracellular enzyme activity, and interactions with other mediators of cellular activity are reviewed. A more detailed review of the actions of eicosanoids as mediators or modifiers of central nervous system physiology and pathophysiology is presented. Recent animal and human studies on the use and alterations of the eicosanoid metabolites is summarized, specifically where they relate to several clinical problem areas of interest to the neurosurgeon and neurobiologist. These areas include cerebrovascular circulation physiology, cerebral ischemia, cerebral vasospasm following subarachnoid hemorrhage, migraine headaches, hypothalamic function, neurotransmission, and nociception. A bibliography of 92 articles for further review is also included.