Ultrasonic vocalization in murine experimental stroke: A mechanistic model of aphasia

作者：Palmateer, Julie; Pan, Jie; Pandya, Arushi; Martin, Lianna; Kumar, Sungita; Ofomata, Adaora; Jones, Theresa A.; Gore, Andrea C.; Schallert, Timothy; Hurn, Patricia D.^*

来源：Restorative Neurology and Neuroscience, 2016, 34(2): 287-295.

DOI：10.3233/RNN-150583

• Cerebral ischemia
• contactin-associated protein 2
• Forkhead box protein 2
• stroke
• ultrasonic vocalization

Purpose: Approximately one-fourth of stroke survivors are aphasic. Speech therapy is the main treatment approach but leaves most patients with chronic disability. Attempts to improve this situation are hampered by a lack of mechanistic understanding of the disability and treatments, reflecting the neglect of this impairment modality in pre-clinical research. Accordingly, we devised a novel murine model of speech-related impairment after stroke to investigate the role of language- and plasticity-associated molecules. Rodents communicate socially with ultrasonic vocalizations (USVs), conveying semantic and semiotic information with complex frequency modulated "songs" and alarm calls. @@@ Methods: Transient focal cerebral ischemia was induced in male C57BL6 mice via either 30 or 45 minutes of reversible right MCAO using the intraluminal filament technique. Nine days post-operatively brains are stained with TTC and analyzed for infarct volume. For behavioral measures health scores are taken (days 1-4), cylinder tests and USV recordings performed at days 3 and 7 post operatively. Real time PCR was performed at 24 and 48 hour and 7 day time points to quantify mRNA expression of communication-related genes (Foxp2, Foxp1, Srpx2, Cntnap2 and Gapdh). Immunohistochemistry was performed to localize FOXP2 protein. @@@ Results: After middle cerebral artery occlusion of either 30 or 45 minutes duration, mice demonstrate profoundly impaired socially evoked USVs. In addition, there is suppression of the language-associated transcription factor, Forkhead box protein 2 (Foxp2), and its downstream binding partner, contactin-associated protein 2 (Cntnap2). @@@ Conclusion: These findings set a foundation for further studies of mechanisms and novel treatment strategies for post-stroke vocalization impairments.

• 出版日期2016
• 单位南京大学