Effect of Gender on Iron-induced Brain Injury in Low Aerobic Capacity Rats

Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Low aerobic capacity is a risk factor for cardiovascular disease and our previous study demonstrated that ICH-induced brain injury is enhanced in rats with low aerobic capacity (low capacity runners; LCRs). We have found that ICH-induced injury is less in female rats compared with that in males. In the present study, we examined the effects of gender on iron-induced brain injury in rats with low aerobic capacity. Adult male and female LCR rats had an intracaudate injection of FeCl2 (50 μl 0.5 mM). T2 Magnetic resonance imaging was carried out at 24 h to determine brain swelling and T2 brain lesion volume. Albumin leakage, an indicator of blood-brain barrier (BBB) disruption, and heme oxygenase-1 (HO-1, a stress marker) levels were determined. Male LCR rats had more severe hemisphere swelling (difference of ipsilateral to contralateral hemisphere volume: 16.6 ± 4.1 vs 11.1 ± 2.6 % in females, p < 0.05) and larger T2 lesion volumes (120 ± 28 vs 87 ± 27 mm(3) in females, p < 0.05) after iron injection. Iron also resulted in more severe BBB disruption in the ipsilateral hemisphere of males (albumin levels: 7,717 ± 1,502 pixels in males vs 5,287 ± 1,342 pixels in females; p < 0.05). The immunoreactivity of HO-1 was also significantly higher in males than females (HO-1/β-actin: 1.31 ± 0.44 vs 1.03 ± 0.05, p < 0.05). Female LCR rats had less iron-induced brain swelling, smaller lesion volumes, and reduced BBB disruption and HO-1 upregulation compared with male LCR rats. This may contribute to the reduced ICH-induced brain injury found in females.