Oxygen radical mechanisms of brain injury following ischemia and reperfusion

Abstract

This review addresses current understanding of oxygen radical mechanisms as they relate to the brain during ischemia and reperfusion. The mechanism for radical production remains speculative in large part because of the difficulty of measuring radical species in vivo. Breakdown of lipid membranes during ischemia leads to accumulation of free fatty acids. Decreased energy stores during ischemia result in the accumulation of adenine nucleotides. During reperfusion, metabolism of free fatty acids via the cyclooxygenase pathway and metabolism of adenine nucleotides via the xanthine oxidase pathway are the most likely sources of oxygen radicals. Although leukocytes have been found to accumulate in some models of ischemia and reperfusion, their mechanistic role remains in question. Therapeutic strategies aimed at decreasing brain injury have included administration of radical scavengers at the time of reperfusion. Efficacy of traditional oxygen radical scavengers such as superoxide dismutase and catalase may be limited by their inability to cross the blood-brain barrier. Lipid-soluble antioxidants appear more efficacious because of their ability to cross the blood-brain barrier and because of their presence in membrane structures where peroxidative reactions can be halted.

Neuroprotective effects of bcl‐2 overexpression in hippocampal cultures: interactions with pathways of oxidative damage

“…This is in contrast to the situation in ischemic brain injury, in which lipid peroxidation is thought to play a more central role in the neuron death (Traystman et al 1991;Chan 1996;Liu et al 1998). However, it is quite plausible that the peroxidative damage could impair functional recovery in surviving neurons.…”

Global Cerebral Ischemia in the Rat: Online Monitoring of Oxygen Free Radical Production Using Chemiluminescence in vivo

“…Indirect strategies to study the role of ROS for ischemic damage have used compounds that inter act with ROS production (particularly ROS scaven gers; for overview see Traystman et al , 1991), and more recently transgenic approaches were used [i. e. , Cu-Zn-SOD overexpressing mice (Kinouchi et al , 1991;Halliwell et al , 1992)]. With very few exceptions, these studies have shown in a number of different ischemia models and species that exper imentally induced increases in the capacity of the brain to cope with oxidative stress are neuroprotec tive.…”

Antioxidant supplementation enhances antioxidant capacity and mitigates oxidative damage following acute ischaemic stroke

“…There is evidence that free radical production is an important mechanism of brain injury after exposure to ischaemia and reperfusion (Traystman et al, 1991). While it is not possible to make direct measurements of antioxidant activity and oxidant damage in this target tissue, concentrations of antioxidants and products of oxidative damage in plasma have proved informative in other studies of stroke (Cherubini et al, 2000;Leinonen et al, 2000).…”

“…There is strong indirect evidence that free radical production is an important mechanism of brain injury after exposure to ischaemia and reperfusion (Traystman et al, 1991).…”

“…Animal models of transient ischaemia/reperfusion in the brain suggest that brain lipids are vulnerable to oxidative attack with accumulation of both conjugated dienes and thiobarbiturate-reactive material during this period (Traystman et al, 1991). This effect is enhanced by poor a-tocopherol (vitamin E) and ascorbic acid (vitamin C) status (Cooper et al, 1980), and can be mitigated by supplementation with vitamin E (Yoshida et al, 1984).…”