Effect of a superoxide dismutase derivative on cold-induced brain edema

Although the involvement of reactive oxygen species has been suggested in the pathogenesis of brain edema, direct evidence supporting this concept is lacking. To elucidate a critical role of oxygen radicals, effect of a superoxide dismutase (SOD) derivative that circulated bound to albumin with a half-life of 6 h on the occurrence of cold-induced brain edema was studied in the rat. When animals were challenged with brain injury by applying a liquid-nitrogen-cold probe to one side of the cerebral hemisphere over the bony skull for 20 s, the vascular permeability of the underlying tissue increased significantly and unilateral brain edema occurred as determined by the accumulation of intravenously injected Evan's blue and the increase in brain weight. Intravenous administration of the SOD derivative markedly suppressed the increase in vascular permeability and the occurrence of brain edema, particularly at their early stages. These and other results suggest that superoxide anion and/or its metabolite(s) might play a critical role in the pathogenesis of traumatic brain injury.