Abstract WP157: Beneficial Effects of Collateral Augmentation by Acetazolamide and Head-Down Tilt in Rat Ischemic Stroke Model

Abstract

Introduction: We investigated whether collateral augmentation treatments with acetazolamide (ACZ), head down tilt (HDT), or combination are effective in rats with the transient middle cerebral artery occlusion (MCAO) models. Methods: All animals were induced MCAO for 1h 30min and reperfusion for 24h. ACZ 100 mg/kg solution in 0.9% saline was administered in a single intravenous bolus of 0.5 ml over 3 min, 30 min after onset of MCAO. HDT was administered using a 15° tilted platform for 60 min, 30 min after onset of MCAO. To measure infarct volume, brain water content and neurological score, 58 male Wistar rats were divided into four groups: control (n=17), ACZ (n=15), HDT (n=13) and combination groups (n=14). Infarction volumes were measured after 2% 2,3,5-triphenyltetrazolium chloride (TTC) staining. Neurologic deficits were assessed using the Garcia and Longa scores at 24h after MCAO. The following formula was used to quantify the brain water content: brain water content (g) = wet brain weight - dry brain weight. Results: The collateral augmentation groups had smaller infarct volume (control, 30.39 ± 8.18 vs. collateral augmentation groups 16.89 ± 11.45, p=0.005) and less brain water content (control, 1.53 ± 0.11 vs. collateral augmentation groups 1.44 ± 0.10, p=0.081). Neurological scores were better in collateral augmentation group than control group (Garcia score; control, 9.8 ± 2.1 vs. collateral augmentation groups, 12.4 ± 3.0, p=0.001) (Longa score; control, 2.5 ± 0.8 vs. collateral augmentation groups, 1.9 ± 1.1, p=0.026). Among groups, the ACZ group was significantly associated with small infarct volume (ACZ, 11.79 ± 5.40 vs. control, 30.39 ± 8.18, p<0.001), followed by the combination group. In addition, the combination group was significantly associated with better neurological scores (Garcia score; combination, 13.33 ± 2.46 vs. control, 9.79 ± 2.12, p=0.017) and less brain water content (combination, 1.35 ± 0.09 vs. control, 1.53 ± 0.11, p=0.031). Conclusion: We found that collateral augmentation was associated with smaller infarction volume and better neurological outcome compared to untreated animal after transient MCAO. Among the treatment methods, the combination group showed the best beneficial effects.