Deferoxamine reduces CSF free iron levels following intracerebral hemorrhage

Abstract

Iron overload occurs in brain after intracerebral hemorrhage (ICH). Deferoxamine, an iron chelator, attenuates perihematomal edema and oxidative stress in brain after ICH. We investigated the effects of deferoxamine on cerebrospinal fluid (CSF) free iron and brain total iron following ICH. Rats received an infusion of 100-microL autologous whole blood into the right basal ganglia, then were treated with either deferoxamine (100 mg/kg, i.p., administered 2 hours after ICH and then at 12-hour intervals for up to 7 days) or vehicle. The rats were killed at different time points from 1 to 28 days for measurement of free and total iron. Behavioral tests were also performed. Free iron levels in normal rat CSF were very low (1.1 +/- 0.4 micromol). After ICH, CSF free iron levels were increased at all time points. Levels of brain total iron were also increased after ICH (p < 0.05). Deferoxamine given 2 hours after ICH reduced free iron in CSF at all time points. Deferoxamine also reduced ICH-induced neurological deficits (p < 0.05), but did not reduce total brain iron. In conclusion, CSF free iron levels increase after ICH and do not clear for at least 28 days. Deferoxamine reduces free iron levels and improves functional outcome in the rat, indicating that it may be a potential therapeutic agent for ICH patients.