Antivasospastic and brain-protective effects of a hydroxyl radical scavenger (AVS) after experimental subarachnoid hemorrhage.

Abstract

The radical scavenger (+/-)-N,N'-propylenedinicotinamide (AVS) was shown recently to ameliorate delayed neurological deficits resulting from ischemia in patients who have had an aneurysmal subarachnoid hemorrhage (SAH). The aim of this study was to evaluate the effect of AVS administration after experimental SAH on 1) behavioral deficits; 2) angiographically confirmed basilar artery (BA) spasm; and 3) blood-brain barrier (BBB) permeability changes. These parameters were measured by 1) using a battery of well-characterized chronic assessment tasks over a 5-day observation period; 2) assessing in vivo the mean vessel diameter 2 days after SAH; and 3) evaluating the extravasation of protein-bound Evans Blue dye by using a spectrophotofluorimetric technique 2 days after SAH. Groups of eight to 10 rats received injections of 400 microl of autologous blood into the cisterna magna. Within 5 minutes after the surgical procedures were completed the rats were treated with an intravenously administered continuous infusion of saline (Group III) or AVS (1 mg/kg/minutes, Group IV). Results were compared with those in sham-operated animals treated with intravenously administered saline (Group I) or AVS (Group II). The AVS-treated rats had significantly improved balance beam scores on Days 1 to 2 (p < 0.05), shorter beam traverse times on Day 1 (p < 0.05), and better beam walking performance on Days 1 to 4 (p < 0.01), but no significant effect was seen in terms of SAH-related changes in body weight. Treatment with AVS also attenuated the SAH-induced BA spasm (p < 0.05) and decreased BBB permeability changes in frontal, temporal, parietal, occipital, and cerebellar cortices, and in the subcortical and cerebellar gray matter and brainstem (p < 0.01). These results demonstrate useful antivasospastic and brain-protective actions of AVS after induction of experimental SAH and provide support for observations of beneficial effects of AVS made in the clinical setting.