Breaking a dogma: acute anti-inflammatory treatment alters both post-lesional functional recovery and endogenous adaptive plasticity mechanisms in a rodent model of acute peripheral vestibulopathy

J Neuroinflammation. 2021 Aug 21;18(1):183. doi: 10.1186/s12974-021-02222-y.

Abstract

Background: Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained spinning vertigo, spontaneous ocular nystagmus and oscillopsia, perceptual-cognitive, posturo-locomotor, and vegetative disorders. We assessed the effectiveness of acute corticotherapy, and the functional role of acute inflammation observed after sudden unilateral vestibular loss.

Methods: We used the rodent model of unilateral vestibular neurectomy, mimicking the syndrome observed in patients with APV. We treated the animals during the acute phase of the vestibular syndrome, either with placebo or methylprednisolone, an anti-inflammatory corticosteroid. At the cellular level, impacts of methylprednisolone on endogenous plasticity mechanisms were assessed through analysis of cell proliferation and survival, glial reactions, neuron's membrane excitability, and stress marker. At the behavioral level, vestibular and posturo-locomotor functions' recovery were assessed with appropriate qualitative and quantitative evaluations.

Results: We observed that acute treatment with methylprednisolone significantly decreases glial reactions, cell proliferation and survival. In addition, stress and excitability markers were significantly impacted by the treatment. Besides, vestibular syndrome's intensity was enhanced, and vestibular compensation delayed under acute methylprednisolone treatment.

Conclusions: We show here, for the first time, that acute anti-inflammatory treatment alters the expression of the adaptive plasticity mechanisms in the deafferented vestibular nuclei and generates enhanced and prolonged vestibular and postural deficits. These results strongly suggest a beneficial role for acute endogenous neuroinflammation in vestibular compensation. They open the way to a change in dogma for the treatment and therapeutic management of vestibular patients.

Keywords: Acute peripheral vestibulopathies; Corticosteroids; Inflammation; Vestibular compensation.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Methylprednisolone / pharmacology
  • Methylprednisolone / therapeutic use*
  • Motor Activity / drug effects
  • Neuronal Plasticity / drug effects*
  • Neuronal Plasticity / physiology
  • Postural Balance / drug effects
  • Rats
  • Rats, Long-Evans
  • Recovery of Function / drug effects*
  • Recovery of Function / physiology
  • Vestibular Neuronitis / drug therapy*
  • Vestibular Neuronitis / physiopathology
  • Vestibular Nuclei / drug effects*
  • Vestibular Nuclei / physiopathology

Substances

  • Anti-Inflammatory Agents
  • Methylprednisolone