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<0.0001), total neurobattery score (p<0.0001), circling (p<0.0001), symmetry of four limbs (p<0.0001), forepaw outstretching (p<0.0001), trunk sensation (p<0.0001), beam-walking (p=0.0003), percent alternation (p=0.0005), bodyweight loss (p=0.006), vibrissae sensation (p=0.0105), and face sensation (p=0.0183). There was not a significant deficit for spontaneous activity or grid-climbing (p>0.05). Among all endpoint metrics, bodyweight loss had the most significant correlation to stroke lesion volume (r=-0.5054, p=0.0005), while beam-walking also had a significant correlation (r=0.2817, p=0.0322). Other metrics did not correlate significantly with stroke lesion volume (p>0.05). Conclusion: Although not commonly viewed as a long-term metric for assessing post-MCAO deficits, bodyweight loss was the most significant predictor of both stroke lesion volume and behavioral deficits in SPAN 2.1 mice. Beam-walking was also a significant predictor of stroke lesion volume and behavioral deficits, though to a lesser extent. While other endpoint metrics were significantly different from baseline data, they did not reliably reflect stroke lesion volume.