Effects of deferoxamine on intracerebral hemorrhage-induced brain injury in aged rats.
OBJECTIVE
Deferoxamine (DFX) reduces brain edema, neuronal death, and neurological deficits after intracerebral hemorrhage (ICH) in young rats. In the present study, we investigated whether DFX is effective on brain injury after ICH in aged rats and examined dose dependency.


METHODS
Male Fischer 344 rats (18 months old) had an intracaudate injection of 100 microL autologous whole blood and were treated with different doses of DFX (10, 50, and 100 mg/kg) or vehicle 2 and 6 hours post-ICH and then every 12 hours up to 7 days. Rats were euthanized at Day 3 for brain edema determination and Day 56 for brain atrophy measurement. Behavioral tests were performed during the experiments.


RESULTS
All 3 doses of DFX attenuated perihematomal brain edema at 3 days (eg, at dose 50 mg/kg, 80.4+/-0.5 versus 81.6+/-0.9% in the vehicle-treated group, P<0.01). Fifty and 100 mg/kg DFX also reduced ICH-induced ventricle enlargement, caudate atrophy, and ICH-induced neurological deficits in aged rats. However, although 10 mg/kg DFX reduced ventricle enlargement and forelimb-placing deficits, it did not reduce caudate atrophy and corner turn deficits.


CONCLUSIONS
These results indicate that DFX can reduce ICH-induced brain injury in aged as well as young rats and that a dose >10 mg/kg is the optimal dose of DFX in this model.
Okauchi
Masanobu
M
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-2200, USA.
Hua
Ya
Y
Keep
Richard F
RF
Morgenstern
Lewis B
LB
Xi
Guohua
G
D000818:Animals; D001284:Atrophy; D001522:Behavior, Animal / Q000502:physiology; D001794:Blood Pressure / Q000502:physiology; D001834:Body Water / Q000502:physiology; D001835:Body Weight / Q000502:physiology; D001921:Brain / Q000473:pathology; D001927:Brain Diseases / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D001929:Brain Edema / Q000209:etiology / Q000473:pathology; D016923:Cell Death; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D002552:Cerebral Ventricles / Q000473:pathology; D003676:Deferoxamine / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005552:Forelimb / Q000502:physiology; D008279:Magnetic Resonance Imaging; D008297:Male; D009474:Neurons / Q000473:pathology; D051381:Rats; D011916:Rats, Inbred F344; D017262:Siderophores / Q000627:therapeutic use*
D017262:Siderophores; D003676:Deferoxamine