ISCHEMIA-INDUCED BRAIN IRON DELOCALIZATION - EFFECT OF IRON CHELATORS

Tissue damage in cerebral ischemia may be produced by acidosis-induced delocalization of intracellular iron which acts as a catalyst in oxid ative reactions. Acidosis was induced either by homogenization and inc ubation of rat cortical homogenates in acidified buffers or by submitt ing hyperglycemic rats to complete ischemia, a procedure that leads to intracellular lactic acidosis. The level of low molecular weight spec ies (LMWS) iron was measured after filtration of tissue homogenates th rough a 10,000 Mr ultrafiltration membrane. When cortical tissue was h omogenized in buffer pH 7, the level of LMWS iron was equal to 0.21 mu g/g. It was significantly enhanced by acidification of the homogeniza tion medium, reaching 0.34 mu g/g at pH 6 and 0.75 mu g/g at pH 5. Whe n the tissue was homogenized in water, the LMWS iron level reached 0.1 7 mu g/g in normoglycemic rats and 0.38 mu g/g (p < .05) in hyperglyce mic rats. Both aerobic incubation of homogenates for 1 h at 37 degrees C and inclusion of EDTA in the homogenization medium led to further i ncreases in the iron level. In order to demonstrate the deleterious ro le of iron in brain ischemia, the effect of treatment with bipyridyl, an iron-chelating agent, was assessed by measuring regional brain edem a by the specific gravity method, 24 h following induction of thrombot ic brain infarction. The treatment significantly attenuated the develo pment of brain edema, reducing the water content of the infarcted area by about 2.5%. Taken together, these results support the hypothesis t hat a significant component of brain ischemic injury involves an iron- dependent mechanism.