Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage.
OBJECTIVE
Previous studies undertaken by the authors have indicated that iron accumulation and oxidative stress in the brain contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study the authors investigate whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury.


METHODS
Male Sprague-Dawley rats each received an infusion of 100 microl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days later. Iron distribution was examined histochemically (enhanced Perls reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Immunohistochemical analysis was performed to investigate 8-hydroxyl-2'-deoxyguanosine (8-OHdG), a marker of oxidative DNA damage, and Western blot analysis was performed to measure the amount of apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage. Iron accumulation was observed in the perihematomal zone from 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in 8-OHdG and APE/Ref-1.


CONCLUSIONS
Deferoxamine and other iron chelators may be potential therapeutic agents for ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.
Nakamura
Takehiro
T
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109-0532, USA.
Keep
Richard F
RF
Hua
Ya
Y
Schallert
Timothy
T
Hoff
Julian T
JT
Xi
Guohua
G
D000818:Animals; D015153:Blotting, Western; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology*; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000188:drug therapy*; D004249:DNA Damage; D003676:Deferoxamine / Q000494:pharmacology*; D004195:Disease Models, Animal; D006406:Hematoma / Q000150:complications; D006801:Humans; D007501:Iron / Q000009:adverse effects / Q000493:pharmacokinetics*; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008297:Male; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D007502:Iron Chelating Agents; D007501:Iron; D003676:Deferoxamine