A New Hippocampal Model for Examining Intracerebral

Background and Purpose—There is an urgent need to develop a model in which to study the mechanism of intracerebral hemorrhage-induced neuronal death in vivo. Methods—This study was divided into 2 parts: (1) Rats received either an infusion of hemoglobin, ferrous iron, or saline into the right hippocampus; (2) Rats had an infusion of hemoglobin and then were treated with either deferoxamine or vehicle. Rats were killed for hippocampus size, DNA damage, and neuronal death measurements. Results—Compared with saline, hemoglobin or iron injection caused hippocampal neuronal death. Systemic use of deferoxamine reduced hemoglobin-induced DNA damage, hippocampal neuronal death, and atrophy. Conclusions—This article demonstrates a new model and indicates that iron has a key role in hemoglobin–induced neuronal death. (Stroke. 2007;38:2861-2863.) Key Words: cerebral hemorrhage hemoglobin iron neuronal death deferoxamine Recently delayed brain atrophy has been found in a ratmodel of intracerebral hemorrhage (ICH),1,2 but ICH-induced neuronal death has been difficult to quantify. It is, therefore, important to develop an ICH model for quantifica-tion of neuronal loss. Both in vivo and in vitro experiments have demonstrated that hemoglobin and iron contribute to brain injury after ICH.3,4 Recent studies have also shown iron overload occurs in the brain after ICH and contributes to ICH-induced DNA damage and brain atrophy.2 However, whether or not hemo-globin causes neuronal death in vivo has not been well studied. The present study develops a new model for examining the mechanisms of ICH-related neuronal death involving injec-tion of hemoglobin or iron into the rat hippocampus. The effects of systemic use of deferoxamine (DFX) on hemoglobin-induced neuronal death were also investigated