Arachidonic Acid Metabolism and Lipid Peroxidation in Stroke: Alpha-Tocotrienol as a Unique Therapeutic Agent

Abstract

Under normal physiological conditions, the human brain has one of the highest metabolic profiles of all organs, using 25% of glucose and 20% of all oxygen consumed by the body. When challenged by metabolic disruption as in ischemic or hemorrhagic stroke, brain tissue that is enriched with arachidonic acid (22:6n - 3 polyunsaturated fatty acid) is highly susceptible to oxidative stress. The consequence of increased generation of radical species in stroke-affected brain tissue is the uncontrolled oxidative metabolism of arachidonic acid, generating a host of secondary products that are culpable neuromodulators of the cell death cascade. In this chapter, preclinical models of ischemic and hemorrhagic stroke injury are explored. Subsequently, the arachidonic acid cascade is examined as a common pathological contributor of oxidative stress in both aforementioned stroke subtypes. Finally, the unique neuroprotective properties of the natural vitamin E alpha-tocotrienol are discussed as a potent intervention of the stroke-induced arachidonic acid cascade.