title: The neuroprotective effect of deferoxamine in the hypoxic-ischemic immature mouse brain.
abstract: The iron chelator deferoxamine is efficacious in ameliorating hypoxic-ischemic brain injury in some models, perhaps by decreasing oxidative stress. Transgenic copper/zinc superoxide dismutase-1 (SOD1) overexpression in neonatal mice increases brain injury after hypoxia-ischemia compared to non-transgenic wildtype littermates because of increased oxidative stress. A neonatal mouse model of hypoxia-ischemia was used to examine histopathological damage, iron histochemistry and free iron concentration in the brains of SOD1 transgenic and non-transgenic littermates. Deferoxamine significantly decreased injury in non-transgenics compared to controls with a trend toward neuroprotection in the transgenics. There was no difference in free iron concentrations in the brains of SOD1 overexpressors or non-transgenics. Deferoxamine may protect the neonatal brain by a number of anti-oxidant mechanisms including iron chelation, enhancement of stress gene expression, or induction of other factors responsible for neuroprotection.
authors.affiliation: Neonatal Brain Disorders Laboratory, Departments of Neurology, University of California-San Francisco, San Francisco, USA.
authors.forename: D P
authors.initials: DP
authors.lastname: Sarco
authors.forename: J
authors.initials: J
authors.lastname: Becker
authors.forename: C
authors.initials: C
authors.lastname: Palmer
authors.forename: R A
authors.initials: RA
authors.lastname: Sheldon
authors.forename: D M
authors.initials: DM
authors.lastname: Ferriero
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D003676:Deferoxamine / Q000494:pharmacology*; D006652:Histological Techniques; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D051379:Mice; D008822:Mice, Transgenic; D018696:Neuroprotective Agents / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics; D000072105:Superoxide Dismutase-1
chemical_list: D018696:Neuroprotective Agents; C000606291:Sod1 protein, mouse; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1; D003676:Deferoxamine