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

Article type: Research Article

Authors: Palmateer, Julie^{a; 1} | Pan, Jie^{a; b; 1} | Pandya, Arushi^c | Martin, Lianna^c | Kumar, Sungita^c | Ofomata, Adaora^c | Jones, Theresa A.^c | Gore, Andrea C.^d | Schallert, Timothy^c | Hurn, Patricia D.^{a; e; *}

Affiliations: [a] Departments of Neuroscience, University of Texas at Austin, Austin, TX, USA | [b] Nanjing University Medical School, Nanjing, PR, China | [c] Departments of Psychology, University of Texas at Austin, Austin, TX, USA | [d] School of Pharmacy, University of Texas at Austin, Austin, TX, USA | [e] University of Texas System, Austin, TX, USA

Correspondence: [*] Corresponding author: Patricia Hurn, Ph.D., Vice Chancellor for Research and Innovation, The University of Texas System, 601Colorado, Suite 211, Austin, TX 78701, USA. Tel.: +1 512 499 4235; Fax: +1 512 499 4371; E-mail: [email protected].

Note: [1] Contributed equally.

Abstract: 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.

Keywords: Cerebral ischemia, contactin-associated protein 2, Forkhead box protein 2, stroke, ultrasonic vocalization

DOI: 10.3233/RNN-150583

Journal: Restorative Neurology and Neuroscience, vol. 34, no. 2, pp. 287-295, 2016