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


METHODS
Male Sprague-Dawley rats received an infusion of 100 microl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days thereafter. Iron distribution was examined histochemically (enhanced Perl reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage, was quantitated by Western blot analysis. Iron accumulation was observed in the perihematoma zone beginning 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in APE/Ref-1.


CONCLUSIONS
Deferoxamine and other iron chelators may be potential therapeutic agents for treating 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; D001479:Basal Ganglia / Q000737:chemistry; D001929:Brain Edema / Q000188:drug therapy* / Q000209:etiology; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism; D015913:Chelation Therapy; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase / Q000032:analysis; D003676:Deferoxamine / Q000494:pharmacology / Q000627:therapeutic use*; D004341:Drug Evaluation; D006406:Hematoma / Q000150:complications / Q000188:drug therapy / Q000378:metabolism; D007501:Iron / Q000032:analysis; D007502:Iron Chelating Agents / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D009419:Nerve Tissue Proteins / Q000032:analysis; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
D007502:Iron Chelating Agents; D009419:Nerve Tissue Proteins; D007501:Iron; C470319:Apex1 protein, rat; D043603:DNA-(Apurinic or Apyrimidinic Site) Lyase; D003676:Deferoxamine