Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage

Abstract

<jats:sec> <jats:title>Object</jats:title> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Male Sprague–Dawley rats received an infusion of 100 μl 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.</jats:p> <jats:p>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.</jats:p></jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>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.</jats:p></jats:sec>

Inflammation after Intracerebral Hemorrhage

“…In support of this possibility, several investigators have shown that nonselective inhibitors of heme oxygenase (tin-mesoporphyrin IX, tin-protoporphyrin, and zinc protoporphyrin) decreased ICH-induced brain injury, including brain edema and neurologic deficits (Gong et al, 2006;Huang et al, 2002;Koeppen et al, 2004;Wagner et al, 2000). Deferoxamine, a ferric iron chelator, was shown to have a similar neuroprotective effect after ICH (Nakamura et al, 2004a;Wan et al, 2006). These findings suggest that ROS could be a potential target for ICH therapy.…”

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibition: Robust New Target or Another Big Bust for Stroke Therapeutics?

“…Further, Richard Keep, Guohau Xi, and coworkers have extensively studied the effects of DFO in autologous blood infusion model of intracerebral hemorrhage and subarachnoid hemorrhage rat models and reported that DFO posttreatment reduces the brain nonheme iron concentration, iron-handling protein expression, oxidative stress, brain edema, neuronal death, and behavioral deficits in rat and piglet models (Nakamura et al, 2004;Gu et al, 2009;Okauchi et al, 2010;Lee et al, 2010).…”

Heme Regulation in Traumatic Brain Injury: Relevance to the Adult and Developing Brain

“…Second, in the adult brain, excess iron can be rapidly sequestered by upregulated iron storage proteins such as ferritin, transferrin, and ceruloplasmin (Patel et al, 2002;Regan et al, 2002;Rouault, 2001). Although iron regulatory capacity may be overwhelmed in the setting of injury, which explains why iron chelators such as deferoxamine have showed neuroprotective benefits (Goldstein et al, 2003;Nakamura et al, 2004). Third, some evidence suggests a role for HO-1 in facilitating the transport of iron out of cells.…”