title: Correlation between afferent rearrangements and behavioral deficits after local excitotoxic insult in the mammalian vestibule: a rat model of vertigo symptoms.
abstract: Damage to inner ear afferent terminals is believed to result in many auditory and vestibular dysfunctions. The sequence of afferent injuries and repair, as well as their correlation with vertigo symptoms, remains poorly documented. In particular, information on the changes that take place at the primary vestibular endings during the first hours following a selective insult is lacking. In the present study, we combined histological analysis with behavioral assessments of vestibular function in a rat model of unilateral vestibular excitotoxic insult. Excitotoxicity resulted in an immediate but transient alteration of the balance function that was resolved within a week. Concomitantly, vestibular primary afferents underwent a sequence of structural changes followed by spontaneous repair. Within the first two hours after the insult, a first phase of pronounced vestibular dysfunction coincided with extensive swelling of afferent terminals. In the next 24 h, a second phase of significant but incomplete reduction of the vestibular dysfunction was accompanied by a resorption of swollen terminals and fiber retraction. Eventually, within 1 week, a third phase of complete balance restoration occurred. The slow and progressive withdrawal of the balance dysfunction correlated with full reconstitution of nerve terminals. Competitive re-innervation by afferent and efferent terminals that mimicked developmental synaptogenesis resulted in full re-afferentation of the sensory epithelia. By deciphering the sequence of structural alterations that occur in the vestibule during selective excitotoxic impairment, this study offers new understanding of how a vestibular insult develops in the vestibule and how it governs the heterogeneity of vertigo symptoms.
authors.affiliation: INSERM U1051, Montpellier 34090, France Sensorion, Montpellier 34000, France gaboyard@yahoo.fr.
authors.forename: Sophie
authors.identifier: 0000-0001-8256-8692
authors.initials: S
authors.lastname: Gaboyard-Niay
authors.affiliation: INSERM U1051, Montpellier 34090, France.
authors.forename: Cécile
authors.initials: C
authors.lastname: Travo
authors.affiliation: Sensorion, Montpellier 34000, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Saleur
authors.affiliation: Sensorion, Montpellier 34000, France.
authors.forename: Audrey
authors.initials: A
authors.lastname: Broussy
authors.affiliation: Sensorion, Montpellier 34000, France.
authors.forename: Aurore
authors.initials: A
authors.lastname: Brugeaud
authors.affiliation: INSERM U1051, Montpellier 34090, France Aix Marseille University UMR 7260, 13331 Marseille, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Chabbert
mesh_terms: D000818:Animals; D001522:Behavior, Animal; D002452:Cell Count; D004195:Disease Models, Animal; D004432:Ear, Middle / Q000187:drug effects / Q000473:pathology; D004848:Epithelium / Q000187:drug effects / Q000473:pathology; D005260:Female; D018069:Hair Cells, Vestibular / Q000473:pathology / Q000648:ultrastructure; D007267:Injections; D007608:Kainic Acid / Q000008:administration & dosage; D008954:Models, Biological; D009475:Neurons, Afferent / Q000187:drug effects / Q000473:pathology*; D009498:Neurotoxins / Q000633:toxicity*; D017208:Rats, Wistar; D013572:Synaptic Vesicles / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D016708:Synaptophysin / Q000378:metabolism; D013997:Time Factors; D014717:Vertigo / Q000473:pathology*; D014722:Vestibule, Labyrinth / Q000294:innervation* / Q000473:pathology* / Q000648:ultrastructure
chemical_list: D009498:Neurotoxins; D016708:Synaptophysin; D007608:Kainic Acid
keywords: Calyx terminals; Excitotoxicity; Functional recovery; Hair cells; Physiopathology; Vestibule