title: Iron toxicity in mice with collagenase-induced intracerebral hemorrhage.
abstract: Intracerebral hemorrhage (ICH) is a devastating form of stroke. In this study, we examined the efficacy of deferoxamine (DFX), an iron chelator, after collagenase-induced ICH in 12-month-old mice. Intracerebral hemorrhage was induced by intrastriatal injection of collagenase. Deferoxamine (200  mg/kg, intraperitoneal) or vehicle was administrated 6  hours after ICH and then every 12  hours for up to 3 days. Neurologic deficits were examined on days 1 and 3 after ICH. Mice were killed after 1 or 3 days of DFX treatment for examination of iron deposition, neuronal death, oxidative stress, microglia/astrocyte activation, neutrophil infiltration, brain injury volume, and brain edema and swelling. Collagenase-induced ICH resulted in iron overload in the perihematomal region on day 3. Systemic administration of DFX decreased iron accumulation and neuronal death, attenuated production of reactive oxygen species, and reduced microglial activation and neutrophil infiltration without affecting astrocytes. Although DFX did not reduce brain injury volume, edema, or swelling, it improved neurologic function. Results of our study indicate that iron toxicity contributes to collagenase-induced hemorrhagic brain injury and that reducing iron accumulation can reduce neuronal death and modestly improve functional outcome after ICH in mice.
authors.affiliation: Department of Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, 720 Rutland Avenue, Baltimore, MD 21205, USA.
authors.forename: He
authors.initials: H
authors.lastname: Wu
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Xueying
authors.initials: X
authors.lastname: Xu
authors.forename: Jessica
authors.initials: J
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D000818:Animals; D001835:Body Weight; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology*; D017364:Collagenases / Q000633:toxicity; D003676:Deferoxamine / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D007249:Inflammation / Q000473:pathology / Q000503:physiopathology; D019190:Iron Overload / Q000378:metabolism / Q000503:physiopathology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D017382:Reactive Oxygen Species / Q000378:metabolism; D020127:Recovery of Function / Q000187:drug effects; D017262:Siderophores / Q000494:pharmacology
chemical_list: D017382:Reactive Oxygen Species; D017262:Siderophores; D017364:Collagenases; D003676:Deferoxamine