Under pathologic conditions such as ischemia or injury, the perturbation of endogenous scavenger enzymes (such as SOD, catalase, etc.) and the overproduction of oxygen radicals may contribute to central nervous system (CNS) injury. The experiments performed here are based on the hypothesis that the pathologic role of oxygen radicals in CNS ischemia and injury is related to alterations in endothelium membrane integrity. Oxygen radical formation by enzymatic as well as non-enzymatic generating systems is known to occur not only in endothelium, but in other brain cells. The experiments reported here demonstrate that exposure of endothelial cells (EC) to free radicals generated by EC incubated in the presence of hypoxanthine (or xanthine) and xanthine oxidase or glucose and glucose oxidase caused alterations in EC permeability, with accompanying changes in cytoskeletal actin filaments. The above effects of endothelium-derived free radicals were both time- and dose-dependent and could be inhibited by treatment with antioxidants. The findings indicate that formation of oxygen metabolites (free radical species) can lead to EC injury and may represent a potential mechanism responsible for alterations in the blood-brain barrier permeability which is known to occur in various neuropathologic disorders, including stroke and multiple sclerosis.
