Abstract DP223: Bodyweight loss is the most significant long-term predictor of both stroke lesion volume and behavioral deficits among mouse models from the Stroke Preclincial Assessment Network.

Background: Behavioral deficits in mouse stroke models are often short-lived and lack significant correlation with stroke lesion volume. These limitations pose a challenge for assessing therapeutic interventions. The Stroke Preclinical Assessment Network phase 2, stage 1 (SPAN 2.1) was a multi-center, multi-stage preclinical study of cerebroprotectants combined with reperfusion. In this study, we explored the most significant long-term metrics for indicating (i) post-MCAO deficits and (ii) stroke lesion volume in mouse models at a single SPAN 2.1 site. Methods: Mice (n=58) from 3 groups of young healthy (~4 mo), diet-induced obese (~4 mo), and aged mice (~17 mo) underwent 60 min MCAO followed by 30 (±2) days of reperfusion. Stroke lesion volume was measured day-3 post-MCAO using MRI. Bodyweight loss, 9-item neurobattery score, corner test turn ratio, Y-maze percent alternation, and PhenoTyper activity (daytime/nighttime movement) were correlated to stroke lesion volume and compared to baseline data. Neurobattery was also analyzed by subtest: spontaneous activity, circling, symmetry of four limbs, forepaw outstretching, trunk sensation, vibrissae sensation, face sensation, beam-walking, and grid-climbing. Baseline PhenoTyper data was not collected. Results: There was a significant deficit between the baseline and turn ratio (p