Effects of the radical scavenger AVS on behavioral and BBB changes after experimental subarachnoid hemorrhage

Abstract

Free radicals are important contributors to the global brain dysfunction that follows subarachnoid hemorrhage (SAH). We evaluated the effects of hydroxyl radical scavenger AVS [(±)-N,N'-propylenedinicotinamide; Nicaraven] after experimental SAH on rodent behavioral deficits (employing a battery of well-characterized assessment tasks over a 2-day observation period) and blood-brain barrier (BBB) permeability changes two days after SAH (quantifying the microvascular alterations according to the extravasation of protein-bound Evans Blue using a spectrophotofluorimetric technique) in dose-response and time-window experiments. Groups of 10 rats were injected with 400 μl of autologous blood into the cisterna magna, and followed by intravenous continuous infusion of saline or 0.1, 0.3 or 1 mg/kg/min of AVS beginning within 5 minutes or 6 or 12 hours after SAH. The results were compared with sham-operated saline-treated and with SAH saline-treated animals. AVS significantly ameliorated performances on Beam Balance (p < 0.01) and decreased BBB permeability changes in frontal, temporal, parietal, occipital and cerebellar cortices and subcortical and cerebellar nuclei and brainstem (p < 0.01), but did not significantly affect changes in Beam Walking. This study demonstrates the neuroprotective effects of AVS when administered after experimental SAH in rats. These effects were dose-dependent and, moreover, were evident within the therapeutic window of 6–12 hours after SAH. These results reinforce the concept of a participation of reactive oxygen intermediates in the cerebral dysfunction following SAH.