Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

Abstract

Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

Microglial Dynamics Modulate Vestibular Compensation in a Rodent Model of Vestibulopathy and Condition the Expression of Plasticity Mechanisms in the Deafferented Vestibular Nuclei

“…Lateral weight distribution was homogenous for the sham group and stable over time. As previously described [ 11 , 61 , 66 , 67 , 74 ], a significant diminution of the laterality index (witnessing an increase of the weight distribution towards the left paws) was observed in the UVN+placebo group compared to the sham group from d7 ( p < 0.01), still present at d30 ( p < 0.001). For the UVN+LPS group, the same pattern was observed with a significant decrease of the laterality index at d14 ( p < 0.05), still present at d30 ( p < 0.01).…”

“…Weight distribution on the lateral axis is a good index of postural stability [ 61 , 66 , 67 , 74 ] and was considered as a laterality index corresponding to the weight distributed on the right paws minus the weight distributed on the left paws ( Figure 6 A). A significant increase in the weight distributed on the left paws was observed during the chronic phase of vestibular compensation.…”

“…Microglial cells are a key component of brain inflammation, involved both in the onset and the resolution of the inflammatory response [ 32 , 37 , 77 ]. It is now known that Unilateral Vestibular Loss (UVL) induces a long-lasting microglial reaction in the deafferented vestibular nuclei (VNs) [ 10 , 11 , 12 , 14 , 74 ]. We recently demonstrated that the pharmacological blockade of the acute inflammatory response after UVN inhibits microglial reaction and alters the expression of the endogenous plasticity mechanisms in the deafferented VNs.…”

L-Thyroxine Improves Vestibular Compensation in a Rat Model of Acute Peripheral Vestibulopathy: Cellular and Behavioral Aspects

“…We demonstrated, in this study, that L-T4 treatment promotes microglial rather than neuronal differentiation. It is interesting to mention that the same result was recently observed in the same UVN rodent model subjected to a sensorimotor rehabilitation protocol [ 79 ]. Likewise, T3 increases the number of microglia cell bodies, promotes microglia survival, and enhances the growth of their processes [ 80 ].…”

“…Like neurogenesis, microglia also appears as a factor interacting with different plasticity mechanisms of the deafferented vestibular environment (excitability, inflammation, neuroprotection, etc.) promoting vestibular function recovery [ 79 ].…”