Effects of Deferoxamine on Intracerebral Hemorrhage-Induced Brain Injury in Aged Rats

Abstract

Background and Purpose-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 L 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, 80.4Ϯ0.5 versus 81.6Ϯ0.9% in the vehicle-treated group, PϽ0.01). 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 Ͼ10 mg/kg is the optimal dose of DFX in this model. (Stroke.

Intracerebral Hematoma Extends via Perivascular Spaces and Perineurium

“…Extensive brain edema and brain damage could occur in either the perihematomal or remote brain regions after ICH, thus leading to neurological deficits (Qureshi et al 2001;Wagner et al 2003;Mun-Bryce et al 2004;Hua et al 2006;Xi et al 2006). Toxic hematoma extravasations, such as iron (Wagner et al 2003;Nakamura et al 2005;Hua et al 2006;Okauchi et al 2009), inflammatory cytokines, and thrombin (Mun-Bryce et al 2004;Xi et al 2006;Zhang et al 2006), contribute to the occurrence of neurological deficits. Nevertheless, the mechanism of how toxic hematoma extravasations cause the remote effects of ICH is still unknown.…”

Early Nonischemic Oxidative Metabolic Dysfunction Leads to Chronic Brain Atrophy in Traumatic Brain Injury

“…One speculation is that the cumulative local toxic effects of iron deposition may lead to oxidative stress and metabolic dysfunction, resulting in greater regional long-term global atrophy. A relationship between iron deposition and atrophy has been seen in primary intracerebral hemorrhage (Okauchi et al, 2009).…”

Antioxidant Strategies in Neurocritical Care

“…In one study, treatment with deferoxamine attenuated death rate and hemorrhagic transformation in a rat model of transient focal ischemia [109]. Treatment with deferoxamine also attenuates the production of ROS, blocks hemoglobin-mediated potentiation of glutamate neurotoxicity, reduces brain malondialdehyde content and induces recovery of sodium-potassium pump activity, and exerts diverse protective effects after experimental ICH [29,33,[110][111][112]. Emerging evidence also supports a potential therapeutic role for deferoxamine following intraventricular and subarachnoid hemorrhages [113,114].…”