Neuroinflammation in central vestibular compensation and in the pathogenesis of vestibular disorders: preclinical evidence, mechanistic bridges, and a causal research agenda

Background Recovery from acute vestibular damage depends on central compensation (plasticity within the vestibular nuclei) rather than on repair of the peripheral lesion. The cellular mechanisms of compensation have classically been framed in neuronal terms; over the past two decades, evidence has accumulated that glial and inflammatory processes participate in the course of compensation and can be manipulated to alter it. Objective To map the evidence for neuroinflammation in central vestibular compensation with explicit attention to its strength, directness, and boundaries, and to derive a falsifiable mechanistic framework and research agenda. Methods Structured PubMed search ([tiab]-restricted queries; 71 unique records screened, 69 on 2 September 2026 and 2 on a 25 October 2026 re-run; 37 included, graded A–E and by directness), supplemented by contextual pools and classic reference studies. Narrative synthesis; not a systematic review. Results Direct evidence is confined to 20 original preclinical studies that measured glial or inflammatory processes in vestibular models: 14 used injury or overload paradigms, in which the question is compensation, and 6 used disease models, which address pathogenesis rather than compensation. In the injury and overload paradigms, glial responses accompany deafferentation and sustained vestibular stimulation; suppressing acute inflammation (methylprednisolone), exacerbating it (LPS), or sustaining it (sleep deprivation through TLR4/NF-κB/NLRP3) all impair compensation, while interventions that alter glial abundance or marker-defined state are associated with improved recovery. In vestibular migraine and ischemic vertigo models, inflammatory pathways contribute to central sensitization. Human brain evidence identified by our structured PubMed search was limited to one TSPO-PET study in vestibular schwannoma; the search identified no direct vestibular-nucleus glial evidence in primary vestibular disorders. Conclusion We propose a dual-phase, state-dependent glial hypothesis: a supportive acute window whose inflammatory level must remain “homeostatic,” followed by a decompensation risk if inflammation persists or polarizes, with a separate, hypothesis-level inflammation-to-sensitization path for vestibular migraine and PPPD. Priority experiments are time-windowed cell-type-specific manipulations in models and TSPO-PET of the vestibular nuclei in acute vestibular neuritis and PPPD. Neuroinflammation is currently best regarded as a candidate modulator of vestibular compensation requiring causal validation, not an established disease mechanism.