title: Ultrasonic vocalization in murine experimental stroke: A mechanistic model of aphasia.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  These findings set a foundation for further studies of mechanisms and novel treatment strategies for post-stroke vocalization impairments.
authors.affiliation: Departments of Neuroscience, University of Texas at Austin, Austin, TX, USA.
authors.forename: Julie
authors.initials: J
authors.lastname: Palmateer
authors.affiliation: Departments of Neuroscience, University of Texas at Austin, Austin, TX, USA.|Nanjing University Medical School, Nanjing, PR, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Pan
authors.affiliation: Departments of Psychology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Arushi
authors.initials: A
authors.lastname: Pandya
authors.affiliation: Departments of Psychology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Lianna
authors.initials: L
authors.lastname: Martin
authors.affiliation: Departments of Psychology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Sungita
authors.initials: S
authors.lastname: Kumar
authors.affiliation: Departments of Psychology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Adaora
authors.initials: A
authors.lastname: Ofomata
authors.affiliation: Departments of Psychology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Theresa A
authors.initials: TA
authors.lastname: Jones
authors.affiliation: School of Pharmacy, University of Texas at Austin, Austin, TX, USA.
authors.forename: Andrea C
authors.initials: AC
authors.lastname: Gore
authors.affiliation: Departments of Psychology, University of Texas at Austin, Austin, TX, USA.
authors.forename: Timothy
authors.initials: T
authors.lastname: Schallert
authors.affiliation: Departments of Neuroscience, University of Texas at Austin, Austin, TX, USA.|University of Texas System, Austin, TX, USA.
authors.forename: Patricia D
authors.initials: PD
authors.lastname: Hurn
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001037:Aphasia / Q000209:etiology*; D004195:Disease Models, Animal; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation / Q000502:physiology*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications*; D017078:Laser-Doppler Flowmetry; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism; D013997:Time Factors; D014828:Vocalization, Animal / Q000502:physiology*
chemical_list: C568163:CNTNAP2 protein, mouse; D051858:Forkhead Transcription Factors; C432917:Foxp1 protein, mouse; C432918:Foxp2 protein, mouse; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D012097:Repressor Proteins
keywords: Cerebral ischemia; Forkhead box protein 2; contactin-associated protein 2; stroke; ultrasonic vocalization