Iron, a hemoglobin degradation product, is associated with lipid peroxidation and free radical formation in the brain after ICH.31 Oxidative DNA damage has been found in the brain after ICH.34 Iron overload plays an important role in many kinds of brain injury such as Alzheimer30 and Parkinson16 diseases. Considering the potential for a massive iron overload in patients with ICH, it is surprising that iron has not been extensively studied as a therapeutic target.
Deferoxamine, an iron chelator, is used to treat hemochromatosis caused by iron toxicity.1 Favorable effects of iron chelator therapy have been reported in various cerebral ischemia models.9,15 In our previous study we found that deferoxamine reduces hemoglobin-induced brain edema.8
Based on the hypothesis that following ICH iron released from the blood clot contributes to brain injury, in the present study we examined the effect of systemic deferoxamine treatment on brain edema and neurological deficits. Intracerebral hemorrhage—induced changes in 8-OHdG and APE (also known as Ref-1) were also examined. Formation of 8-OHdG is used as a marker of oxidative DNA damage.10 Immunoreactivities to 8-OHdG can be useful for evaluating oxidative damage.33 Apurinic/apyrimidinic endonuclease/redox effector factor—1 is a multifunctional protein in the DNA base excision repair pathway and is responsible for repairing AP sites in DNA after oxidative DNA damage.2,14 Reductions in this protein have been found in forms of brain injury that are associated with oxidative stress.14 We hypothesized that such changes in ICH might be prevented by deferoxamine.
This study was supported by Grant Nos. NS-17760 (J.T.H.) and NS-39866 (G.X.) from the National Institutes of Health.