• C Imperatore, A Germanò, D d'Avella, F Tomasello, and G Costa.
• Institute of Pharmacology, University of Messina, Italy.
• Life Sci. 2000 Jan 21; 66 (9): 779-90.

AbstractFree 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 microl of autologous blood into the cisterna magna, and followed by intravenous continuous infusion of saline or 0.1, 03 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.

26 keywords...

hide…