title: 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.
authors.affiliation: Department of Neurosurgery, Hanyang University Medical Center, Seoul, Korea.
authors.forename: Hyoung-Joon
authors.initials: HJ
authors.lastname: Chun
authors.forename: Dong Won
authors.initials: DW
authors.lastname: Kim
authors.forename: Hyeong-Joong
authors.initials: HJ
authors.lastname: Yi
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Eun Hyun
authors.initials: EH
authors.lastname: Kim
authors.forename: Se Jin
authors.initials: SJ
authors.lastname: Hwang
authors.forename: Cheol-Su
authors.initials: CS
authors.lastname: Jwa
authors.forename: Yoon Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Hyunchul
authors.initials: H
authors.lastname: Ryou
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D039481:CD11b Antigen / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000150:complications*; D003676:Deferoxamine / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005121:Extremities / Q000503:physiopathology; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D006406:Hematoma / Q000188:drug therapy / Q000209:etiology; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage*; D008297:Male; D009422:Nervous System Diseases / Q000188:drug therapy* / Q000209:etiology*; D011597:Psychomotor Performance / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017262:Siderophores / Q000008:administration & dosage*; D013037:Spatial Behavior / Q000187:drug effects
chemical_list: D039481:CD11b Antigen; D005904:Glial Fibrillary Acidic Protein; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D017262:Siderophores; D003676:Deferoxamine