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 microL 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, 80.4+/-0.5 versus 81.6+/-0.9% in the vehicle-treated group, P<0.01). 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 >10 mg/kg is the optimal dose of DFX in this model.

Figures

Figure 1

Bar graph showing brain water (A), sodium (B) and potassium (C) content at 3 days after ICH. Values are expressed as the means ± SD. Contra = contralateral, Ipsi = ipsilateral, Cerebel = cerebellum. *p

Figure 2

Bar graph displaying body weight reduction during the experiment. Values are expressed as the means ± SD.

Figure 3

Forelimb placing (A) and corner turn (B) test scores prior to ICH, and 1, 28, 56 days after ICH. Values are expressed as the means ± SD. *p

Figure 4

A: T2-weighted magnetic resonance images at 2 months after ICH treated with vehicle or DFX 50 mg/kg. B: Bar graph demonstrating the ventricle volume expressed as a percentage of the contralateral side. Values are expressed as the means ± SD. *p<0.05, #p<0.01 vs. ICH + Vehicle group.

Figure 5

A: Coronal gross H&E sections eight weeks after ICH treated with vehicle or DFX 50 mg/kg. B: Bar graph demonstrating caudate size expressed as a percentage of the contralateral side. Values are expressed as the means ± SD. *p