Protective effect of the iron chelator deferoxamine on cold-induced brain edema

Abstract

Oxygen free radicals such as superoxide radical and iron-catalyzed hydroxyl radical generated by the superoxide system have been implicated in the genesis of brain edema. Therefore, deferoxamine (DFO), an iron chelator, could potentially be used to treat brain edema. To examine this hypothesis, vasogenic brain edema was produced in 48 cats by a cortical freezing lesion. The animals were separated into three groups: Group 1 comprised 14 cats that received no DFO and were sacrificed at 6 or 24 hours; Group 2 consisted of 12 cats that were treated with DFO (50 mg/kg/ml, intravenously) at 15 minutes before the lesion was made and 60 minutes later and were sacrificed at 6 or 24 hours; and Group 3 included 12 cats that were treated with DFO (50 mg/kg/ml, intravenously) at 15 minutes after the lesion was produced and 60 minutes later and were sacrificed at 6 or 24 hours. The effect of DFO on arterial blood pressure was also studied in the remaining 10 cats. Brain water content in eight sampling areas was measured by the specific gravity method. Blood-brain barrier disruption was assessed by spread of Evans blue dye with planimetry. Specific gravity values at 6 and 24 hours were significantly higher in Group 2 than in Group 1 animals. Areas of Evans blue dye extravasation at 6 and 24 hours were significantly reduced in Group 2 relative to Group 1. Group 3 cats showed improvement in specific gravity values and Evans blue extravasation at 6 hours, but not at 24 hours. The iron chelator DFO prevented early development of brain edema; thus, this oxygen free radical scavenger may provide a foundation for a new therapy for brain edema.