title: Deferoxamine reduces neuronal death and hematoma lysis after intracerebral hemorrhage in aged rats.
abstract: Intracerebral hemorrhage (ICH) is primarily a disease of the elderly. Deferoxamine (DFX), an iron chelator, reduces long-term neurological deficits and brain atrophy after ICH in aged rats. In the present study, we investigated whether DFX can reduce acute ICH-induced neuronal death and whether it affects the endogenous response to ICH (ferritin upregulation and hematoma resolution) in aged rats. Male Fischer 344 rats (18 months old) had an intracaudate injection of 100 μL autologous whole blood into the right basal ganglia and were treated with DFX (100 mg/kg) or vehicle 2 hours post-ICH and then every 12 hours up to 7 days. Rats were euthanized 1, 3, or 7 days later for neuronal death, ferritin and hematoma size measurements. Plasma ferritin levels and behavioral outcome following ICH were also examined. DFX treatment significantly reduced ICH-induced neuronal death and neurological deficits. DFX also suppressed ferritin upregulation in the ipsilateral basal ganglia after ICH and hematoma lysis (hematoma volume at day 7: 13.2±4.9 vs. 3.8±1.2 mm3 in vehicle-treated group, p<0.01). However, effects of DFX on plasma ferritin levels after ICH did not reach significance. In conclusion, DFX reduces neuronal death and neurological deficits after ICH in aged rats. It also affects the endogenous response to ICH.
authors.affiliation: Department of Neurosurgery, University of Michigan, USA ; Department of Neurological Surgery, Kagawa University, Japan.
authors.forename: Tetsuhiro
authors.initials: T
authors.lastname: Hatakeyama
authors.forename: Masanobu
authors.initials: M
authors.lastname: Okauchi
authors.forename: Ya
authors.initials: Y
authors.lastname: Hua
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
mesh_terms: D000367:Age Factors; D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002543:Cerebral Hemorrhage / Q000188:drug therapy* / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D004195:Disease Models, Animal; D005293:Ferritins / Q000097:blood; D006406:Hematoma / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009474:Neurons / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D017262:Siderophores / Q000627:therapeutic use*
chemical_list: D017262:Siderophores; D005293:Ferritins; D003676:Deferoxamine
keywords: Cerebral hemorrhage; deferoxamine; iron; neuronal death