Abstract 11: Ultrasonic Vocalizations as a Tool to Model Aphasia in Murine Experimental Stroke

Abstract

BACKGROUND: Stroke is the leading cause of aphasia. One in four stroke survivors experience some form of speech impairment. Although rodents do not produce speech like humans, male mice vocalize at ultrasonic frequencies. By analyzing changes in ultrasonic vocalization (USV) patterns we assessed correlates of speech impairment in the rodent model. Further, to identify for any lateralization effect in vocalization we compared left and right sided strokes. Finally, changes in FOXP2 expression, a gene involved in the language production, were assessed. METHODS: Stroke was induced by 60-min middle cerebral artery occlusion (MCAO) in male C57BL/6 mice. All mice were pre-screened for baseline USVs one day prior to stroke, with an ultrasonic microphone and amplifier from Avisoft Bioacoustics for two 120-second trials, and analyzed using SAS-lab Pro. The first cohort determined if stroke led to changes in USVs and were tested on the day of stroke, post-stroke day (psd) 2, 7 and 14. The second cohort was used to assess differences between left and right MCAO (LMCAO/RMCAO) and shams, USVs were recorded psd 1 and 3. “High vocalizing” mice (>30 USVs / 120sec) were used to avoid baseline bias (n=45). FOXP2 levels were assessed by western blot at 6 and 24 hrs after stroke. RESULTS: Repeated measures ANOVA revealed a significant effect of stroke on USVs across the days [F(1,8)=8.181; p<0.05] in the first cohort. Stroke reduced USVs on psd 2 and psd 7, but mice recovered to sham levels by psd 14. Results from the second cohort identified that, on psd1 LMCAO mice had significantly reduced USVs compared to mice subjected to RMCAO (p<0.10), and RMCAO mice vocalized less than sham mice (p<0.05). Infarct analysis showed no difference between RMCAO and LMCAO. Shams showed full recovery to baseline USVs by psd 3. FOXP2 levels were elevated at 6 hrs after stroke, but fell to below sham levels at 24 hrs. CONCLUSIONS: The findings of this study suggest that screening for USVs may offer a novel tool for post-stroke behavioral recovery assessment. Stroke induced differential changes in USVs between RMCAO and LMCAO indicate lateralization of vocalization in rodents. In conclusion, decreased USVs parallels FOXP2 expression at 24 hrs suggests that rodent MCAO could be a practical model to study aphasia.