Deferoxamine Alleviates Iron Overload and Brain Injury in a Rat Model of Brainstem Hemorrhage

BACKGROUND: Brainstem hemorrhage (BSH) is the most dangerous and devastating subtype of intracerebral hemorrhage and is associated with high morbidity and mortality. However, to date, no effective prevention methods or specific therapies have been available to improve its clinical outcomes. We preliminarily explored the efficacy of deferoxamine (DFO), a clinical chelator known for its iron-scavenging activities, in a rat model of BSH induced with collagenase infusion. METHODS: DFO or saline was administrated 6 hours after BSH induction and then every 12 hours for <= 7 days. The survival curve of the rats was created, and the neurological scores were examined on days 1, 3, and 7 after BSH. The rats were sacrificed after 1, 3, and 7 days of DFO treatment for histological examination and immunohistochemistry. RESULTS: The results showed that administration of DFO delayed erythrocytes lysis, reduced iron deposition, reduced reactive oxygen species generation, reduced heme oxygenase-1 expression, and alleviated brain injury such as neuron degeneration and myelin sheath injury. However, DFO did not improve the survival rate and neurobehavioral outcomes in this model. CONCLUSIONS: Administration of DFO had limited therapeutic effects on collagenase-induced brainstem hemorrhage in rats. Some potential explanations were proposed, and more preclinical work is required to clarify the controversial curative effect of DFO in ICH.