Central and peripheral plasticity after chemical unilateral labyrinthectomy: Glial responses, calyces dynamics, and behavioral consequences

Peripheral vestibular disorders are highly prevalent, but the underlying neurobiological mechanisms remain poorly understood, particularly regarding bilateral peripheral plasticity following unilateral injury. Using a rat model of chemical unilateral labyrinthectomy (cUL) (SHAM, n = 14; cUL, n = 20), we combined behavioral analyses, auditory assessments, immunohistochemistry, and histological quantification to characterize central and peripheral adaptations from 1 to 30 days after vestibular deafferentation. cUL induced significant postural deficits from day 1, while hyperactivity and anxiety-like behaviors emerged from day 9 and persisted over time. In the deafferented medial vestibular nucleus, robust glial reactivity developed rapidly (day 3) whereas only astrocytes remained significantly elevated throughout the observation period. Histological analyses revealed a marked loss of type I hair cell calyces in the ipsilateral utricle to ototoxic exposure at both acute (D3) and chronic (D30) time points. Unexpectedly, the contralateral utricle also exhibited a transient reduction in calyceal endings at D3 (p < 0.01), which recovered by D30, revealing previously unrecognized bilateral peripheral vestibular plasticity following unilateral vestibular injury. In contrast, cochlear alterations remained restricted to the ipsilateral side of ototoxic exposure indicating distinct adaptive responses in the auditory and vestibular organs. Together, these findings demonstrate that unilateral vestibular injury triggers coordinated central glial reactivity and contralateral peripheral vestibular plasticity, providing new insight into the cellular mechanisms underlying vestibular compensation.