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LOCAL CONTROL OF CIRCULATION

Neuroprotection by tempol in a model of iron-induced oxidative stress in acute ischemic stroke

¹Department of Physiology, Medical College of Georgia; and ²Department of Clinical and Administrative Sciences, University of Georgia, Medical College of Georgia, Augusta, Georgia 30912

Submitted 23 July 2002 ; accepted in final form 20 October 2003

Studies suggest iron exacerbates the damage caused by ischemic stroke. Our aim was to elucidate the effect of iron overload on infarct size after middle cerebral artery occlusion (MCAO) and to evaluate the efficacy of tempol, a superoxide dismutase mimetic, as a neuroprotective agent. Rats were administered iron ± tempol before MCAO; control rats received saline. The middle cerebral artery was occluded for 24 h, and the size of the resultant infarct was assessed and expressed as the percentage of the hemisphere infracted (%HI). Iron treatment increased infarct size compared with control (51.83 ± 3.55 vs. 27.56 ± 3.28%HI iron treated vs. control, P = 0.01); pretreatment with tempol reversed this (51.83 ± 3.55 vs. 26.09 ± 9.57%HI iron treated vs. iron + tempol treated, P = 0.02). We hypothesized that reactive oxygen species (ROS) were responsible for the iron-induced damage. We measured ROS generated by exogenous iron in brain and peripheral vasculature from rats that had not undergone MCAO. There was no increase in ROS production in the brain of iron-treated rats or in brain slices incubated with iron citrate. However, ROS generation in carotid arteries incubated with iron citrate was significantly increased. ROS generation from the brain was assessed after MCAO by dihydroethidine staining; there was a dramatic increase in the ROS generation by the brain in the iron-treated rats compared with control 30 min after MCAO. We propose that iron-induced ROS generation in the cerebral vasculature adds to oxidative stress during an ischemic episode after the disruption of the blood-brain barrier.

cerebral vasculature; iron overload; reactive oxygen species; cerebral ischemia

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