Deferoxamine treatment for intracerebral hemorrhage in aged rats: therapeutic time window and optimal duration.
OBJECTIVE
Deferoxamine (DFX) reduces brain edema, neurological deficits, and brain atrophy after intracerebral hemorrhage (ICH) in aged and young rats. Our previous study found that 50 mg/kg is an effective dose in aged rats. In the present study, we explored potential therapeutic time windows and optimal therapeutic durations.


METHODS
Aged male Fischer 344 rats (18 months old) sustained an intracaudate injection of 100 microL autologous whole blood, followed by intramuscular DFX or vehicle beginning at different time points, or continuing for different durations. Subgroups of rats were euthanized at day 3 for brain edema measurement and day 56 for brain atrophy determination. Behavioral tests were performed on days 1, 28, and 56 after ICH.


RESULTS
Systemic administration of DFX, when begun within 12 hours after ICH, reduced brain edema. DFX treatment started 2 hours after ICH and administered for >or=7 days attenuated ICH-induced ventricle enlargement, caudate atrophy, and neurological deficits. DFX attenuated ICH-induced brain atrophy and neurological deficits without detectable side effects when begun within 24 hours and administered for 7 days.


CONCLUSIONS
To the extent that these results can be translated to humans, the therapeutic time window and the optimal duration for DFX in this aged rat model of ICH may provide useful information for an ongoing DFX-ICH clinical trial.
Okauchi
Masanobu
M
Department of Neurosurgery, University of Michigan, Ann Arbor, Mich 48109-2200, USA.
Hua
Ya
Y
Keep
Richard F
RF
Morgenstern
Lewis B
LB
Schallert
Timothy
T
Xi
Guohua
G
D000375:Aging / Q000502:physiology*; D000818:Animals; D001284:Atrophy / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D002421:Caudate Nucleus / Q000098:blood supply / Q000187:drug effects / Q000473:pathology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology* / Q000627:therapeutic use; D004195:Disease Models, Animal; D004334:Drug Administration Schedule; D020547:Lateral Ventricles / Q000187:drug effects / Q000473:pathology; D008297:Male; D001523:Mental Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D051381:Rats; D011916:Rats, Inbred F344; D017262:Siderophores / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D017262:Siderophores; D003676:Deferoxamine