The combination of deferoxamine and minocycline strengthens neuroprotective effect on acute intracerebral hemorrhage in rats

Objectives: Intracerebral hemorrhage (ICH) is a devastating type of strokes that carries high mortality rates, but effective therapeutic options are still lacking. Here, the adult rat model of ICH was used to investigate the efficacy of a combinational therapy of deferoxamine (DFX) and minocycline.Methods: The ICH was induced by stereotaxic infusion of collagenase into striatum of adult rats. After the induction of ICH, rats were treated with intraperitoneal injection of deferoxamine (50 mg/kg), minocycline (45 mg/kg), or both agents, at 2 hours after ICH and then every 12 hours for up to 3 days. The vehicle group were treated with phosphate-buffered saline (PBS) only. Rats were killed at 1, 2, and 3 day(s) for examination of iron deposition, neuronal death, neurological deficits, the area of brain damage, activation of microglia/macrophages.Results: Our data revealed that the systemic administration of DFX and/or minocycline decreased iron accumulation. And immunofluorescence staining results indicated that drug-treated group significantly decreased the neuronal degeneration, the number of activated microglia/macrophages and the amount of cell death after ICH. In addition, neurological deficits caused by ICH were improved in the presence of DFX and/or minocycline compare with vehicle group. Furthermore, the combination treatment showed better effects in neuroprotection and anti-inflammation when compared to the monotherapy groups.Conclusions: The combination therapy significantly reduces the number of neuronal deaths, suppresses of the activation of microglia/macrophages, decreases iron accumulation in the area around the hematoma, lessening the brain damage area, and improving neurological deficits in ICH.