New mouse model for inducing and evaluating unilateral vestibular deafferentation syndrome

Background: Unilateral vestibular deafferentation syndrome (uVDS) holds a particular place in the vestibular pathology domain. Due to its suddenness, the violence of its symptoms that often result in emergency hospitalization, and its associated original neurophysiological properties, this syndrome is a major source of questioning for the otoneurology community. Also, its putative pathogenic causes remain to be determined. There is currently a strong medical need for the development of targeted and effective countermeasures to improve the therapeutic management of uVDS. New methods: The present study reports the development of a new mouse model for inducing and evaluating uVDS. Both the method for generating controlled excitotoxic-type peripheral vestibular damages, through transtympanic administration of the glutamate receptors agonist kainate (TTK), and the procedure for evaluating the ensuing clinical signs are detailed. Comparison with existing methods: Through extensive analysis of the clinical symptoms characteristics, this new animal model provides the opportunity to better follow the temporal evolution of various uVDS specific symptoms, while better appreciating the different phases that composed this syndrome. Results: The uVDS evoked in the TTK mouse model displays two main phases distinguishable by their kinetics and amplitudes. Several parameters of the altered vestibular behaviour mimic those observed in the human syndrome. Conclusion: This new murine model brings concrete information about how uVDS develops and how it affects global behaviour. In addition, it opens new opportunity to decipher the etiopathological substrate of this pathology by authorizing the use of genetically modified mouse models. (C) 2017 Elsevier B.V. All rights reserved.