Animal models and molecular markers for cerebral ischemia-reperfusion injury in brain

Abstract

The brain which constitutes about 2% of the total body weight in humans receives 20% of the cardiac output and accounts for 20% of the total oxygen consumption. ~ Owing to the high metabolic rate, normal brain function depends not only on a constant supply of oxygen but also on a continuing supply of glucose from the blood. The brain has limited stores of glucose and glycogen and lacks the ability to oxidize free fatty acids through 3-ketothiolase. 2 These metabolic features render the brain vulnerable to injury arising from disturbances in blood flow, such as those that occur during cerebral ischemia. Cerebral ischemia may occur in conditions such as head trauma, subarachnoid hemorrhage, stroke, and cardiac arrest. During reperfusion following ischemia (where the oxygen supply is restored to the brain), maximal damage to the tissue is observed, which may be primarily attributed to oxidative stress,3 in addition to other factors such as altered glycolysis and disruption of the blood-brain barrier. The source of reactive oxygen species (ROS) include products from mitochondrial respiration, the arachidonic acid cascade, xanthine-xanthine oxidase, 4 and excitatory amino acids. 5 The brain is rich in polyunsaturated fatty acids, and the ROS promote lipid peroxidation.