ABSTRACT NUMBER: ESOC2026A764 GLYCEMIC VARIABILITY REDUCTION AS A THERAPEUTIC APPROACH AFTER STROKE: FINDINGS FROM A REPERFUSION MODEL (THE GLIAS-III STUDY)

Abstract Background and aims Previous trials addressing poststroke hyperglycemia have shown negative results, likely due to heterogenous populations and attempts at intensive glucose reduction. We aimed to evaluate whether reducing glycemic variability (GV) through intravenous insulin administration is associated with improved recovery in a rat model of ischemic stroke with reperfusion. Methods Twenty-five male and female Sprague-Dawley rats were randomly allocated to the following groups: Sham, Control (stroke+hyperglycemia) and Stroke+hyperglycemia+intravenous insulin treatment (3U/day for 5 days). Cerebral ischemia was induced by transient middle cerebral artery occlusion for 60 minutes. GV was calculated as the standard deviation of blood glucose levels obtained over five days, with four measurements per day. Motor function was assessed using the Ledged Beam Walking test at 24, 48, 72 and 96 hours after stroke. Lesion volume and levels of VEGF, NeuN and GFAP in the perilesional area were assessed at 96 hours by T2 and immunofluorescence, respectively. Results Treated animals showed lower GV [(43.75±15,58 vs. 125.30±35.77); p=0.032], improved functional outcome [(22.71±1.37 vs. 31.29 ±0.47); p=0.035] and reduced infarct volume [(28.70±5.26 vs. 34.76±4.52); p=0.011] at 96 hours compared to control. In addition, intravenous treatment significantly increased VEGF expression [(148,575.82±6,453.53 vs. 85,230.92 ±7,974.12); p=0.001], NeuN [(301.35±18.8 vs. 247.00±13.23); p=0.018] and reduced GFAP expression [(41,919.00±2,634.21 vs. 85,230.92±7,974.12) p=0.008] at 96 hours after stroke. Conclusions Intravenous insulin treatment reduces GV, which appears to be associated with improved recovery and brain protection after ischemic stroke with reperfusion. Conflict of interest Javier Pozo-Novoa: nothing to disclose.