ANTIVASOSPASTIC AND BRAIN-PROTECTIVE EFFECTS OF A HYDROXYL RADICAL SCAVENGER (AVS) AFTER EXPERIMENTAL SUBARACHNOID HEMORRHAGE

Object. The radical scavenger (+/-)-N,N'-propylenedinicotinamide (AVS) was shown recently to ameliorate delayed neurological deficits result ing 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-b rain barrier (BBB) permeability changes. Methods. These parameters wer e measured by 1) using a battery of well-characterized chronic assessm ent tasks over a 5-day observation period; 2) assessing in vivo the me an vessel diameter 2 days after SAH; and 3) evaluating the extravasati on of protein-bound Evans Blue dye by using a spectrophotofluorimetric technique 2 days after SAH. Groups of eight to 10 rats received injec tions of 400 mu l of autologous blood into the cisterna magna. Within 5 minutes after the surgical procedures were completed the rats were t reated with an intravenously administered continuous infusion of salin e (Group III) or AVS (1 mg/kg/minutes, Group IV). Results were compare d with those in sham-operated animals treated with intravenously admin istered saline (Group I) or AVS (Group II). The AVS-treated rats had s ignificantly improved balance beam scores on Days 1 to 2 (p < 0.05), s horter beam traverse times on Day 1 (p < 0.05), and better beam walkin g performance on Days 1 to 4 (p < 0.01), but no significant effect was seen in terms of SAM-related changes in body weight. Treatment with A VS also attenuated the SAM-induced BA spasm (p < 0.05) and decreased B BB permeability changes in frontal? temporal, parietal, occipital, and cerebellar cortices, and in the subcortical and cerebellar gray matte r and brainstem (p < 0.01). Conclusions. These results demonstrate use ful antivasospastic and brain-protective actions of AVS after inductio n of experimental SAH and provide support for observations of benefici al effects of AVS made in the clinical setting.