Effects of statin and deferoxamine administration on neurological outcomes in a rat model of intracerebral hemorrhage

Abstract

Deferoxamine (DFX), a potent iron-chelating agent, reduces brain edema and neuronal cell injury that develop due to the hemolysis cascade. Statins have neuroprotective effects via anti-inflammatory action and increment of cerebral blood flow after intracerebral hemorrhage (ICH). The purpose of this study was to identify the effects of combined DFX and statins treatment in an experimental ICH rat model. The treatments were: intraperitoneal (i.p.) injection of DFX (group I), combined treatment of i.p. DFX and oral statins (group II), statins only (group III) and treatment with vehicle (group IV). Induction of ICH was performed with injection of bacterial collagenase type IV into the left striatum. After removal of the brain, hematoma volume, water content and brain atrophy were measured. Immunohistochemistry in the perihematomal region was performed for identification of microglial infiltration, astrocyte expression and apoptotic cell presence. Statistical analysis was performed using the non-parametric Kruskal-Wallis test and significance was evaluated when the p value was less than 0.05. According to behavioral tests, significant differences among treatment groups were noted 4 weeks after ICH induction (p < 0.05). However, there were no significant differences among treatment groups in hematoma volume, brain water content or brain atrophy. In the perihematomal area, the activated microglial cells were reduced in the combined treatment group. Among the four groups, a significant difference in immunohistochemical staining was identified (p < 0.05). These results suggest that combined treatment with DFX and statins improves neurologic outcomes after ICH through reduction of microglial infiltration, apoptosis, inflammation and brain edema.

Statins in Intracerebral Hemorrhage

“…A variety of preclinical studies have shown improved functional outcome, reduced peri-hematomal edema, preserved blood brain barrier, promoted synaptogenesis, and decreased inflammatory reaction and perihematomal cell death in experimental ICH in rodents [47][48][49][50][51][52]. One should keep in mind that in most of these studies, very high dosages of statins are used-that is, dosages that go beyond current recommendations, if translated into the human setting.…”

Curcumin attenuates brain edema in mice with intracerebral hemorrhage through inhibition of AQP4 and AQP9 expression

“…Iron overload caused by ICH is an important contributor to neurobiological deficits, brain edema, inflammation, neuron apoptosis and brain atrophy. These effects can be reduced with deferoxamine, an iron chelator [38][39][40][41][42][43][44][45] . However, two studies [46,47] have reported that deferoxamine reduces the level of iron, but does not improve outcomes, in a collagenase-induced ICH model.…”

Intracerebral Hemorrhage: Perihemorrhagic Edema and Secondary Hematoma Expansion: From Bench Work to Ongoing Controversies

“…Combination of granulocyte-colony stimulating factor (G-CSF) and statins further enhance their neuroprotective capacity with less cell apoptosis than with either agents alone (94). Combination of statins and deferoxamine showed a greater effect on PHE and hematoma volume than either agent alone (95). Unlike animal studies, statin use in humans has been linked to increased PHE volume in ICH patients with no effect on CBF (96).…”