Iron intake increases infarct volume after permanent middle cerebral artery occlusion in rats

Experimental and clinical data suggest an important role of iron in cerebral ischaemia. We measured infarct volume and analysed the oxidative stress, and also the excitatory and inflammatory responses to brain injury in a rat stroke model after an increased oral iron intake. Permanent middle cerebral artery occlusion (MCAO) was performed in ten male Wistar rats fed with a diet containing 2.5% carbonyl iron for 9 weeks, and in ten control animals. Glutamate, interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-alpha) were determined in blood samples before and at 2, 4, 6, 8, 24 and 48 h after MCAO, and thiobarbituric acid reaction substances (TBARS) were analysed at 48 h. Infarct volume was measured at 48 h by image analysis on brain slices stained with 1% TTC. Tissue iron was measured 3 by atomic absorption spectrophotometry. Infarct volume was 66% greater in the iron fed rats than in the control group (178+/-49 mm(3) 3 versus 107+/-53 mm(3), p<0.01). Significant higher levels of glutamate, IL-6 and TNF-alpha were observed in the group with iron intake (peak values were obtained at 6, 8 and 4 It, respectively). Iron-fed animals also showed significantly higher levels of TBARS than those receiving a normal diet (6.52+/-0.59 vs. 5.62+/-0.86 mumol/l, P=0.033) Liver iron stores (3500+/-199 vs. 352+/-28 mug Fe/g, P<0.0001), but not brain iron stores (131 vs. 139 mug Fe/g, P=0.617), were significantly higher in the iron fed rats group. These results suggest that iron intake is associated with larger infarct volumes after MCAO in the rat. This effect seems to be associated with higher oxidative stress, excitotoxicity and inflammatory responses. (C) 2002 Elsevier Science B.V. All rights reserved.