Neuroinflammation and neural activity in the olfactory bulb drives olfactory dysfunction in a rat model of eosinophilic chronic rhinosinusitis

BACKGROUND: Chronic rhinosinusitis (CRS) is a common cause of olfactory dysfunction (OD), and eosinophilic CRS is one of the subtypes characterized by eosinophilic infiltration. Animal models of olfactory dysfunction in eosinophilic CRS are necessary for exploring potential therapeutic strategies. Glucocorticoids are therapeutic for eosinophilic CRS-OD and the mechanism of action requires further exploration. METHODOLOGY: The eosinophilic CRS-OD rat model was induced by intranasal administration of ovalbumin (OVA) and Aspergillus oryzae protease (AP) for 8 weeks, followed by intraperitoneal injection of dexamethasone. Olfactory function was assessed behaviorally, neuronal activity electrophysiologically, and neurotransmitter/inflammatory factor levels via high-performance liquid chromatography (HPLC). Histological analyses of nasal tissue and the olfactory bulb were performed. RESULTS: All OVA/AP-induced eosinophilic CRS-OD rats developed chronic nasal inflammation and olfactory dysfunction. Reduced olfactory bulb (OB) volume was accompanied by thinning of the olfactory neuron layer (ONL) and the glomerular layer (GL). The OB exhibited increased microglia and elevated inflammatory cytokine expression. Further analysis revealed decreased glutamate (Glu), increased γ-aminobutyric acid (GABA), and a significant reduction in the spontaneous firing rate (SFR) of mitral/tufted cells (M/Ts) within the OB. Dexamethasone treatment significantly ameliorated olfactory impairment in this model, decreasing OB microglia numbers and inflammatory cytokine levels, and significantly increasing M/T SFR. CONCLUSIONS: Microglia-mediated neuroinflammation contributes to abnormal neural activity in the olfactory bulb, which may be one mechanism for the development of eosinophilic CRS-OD. The neuroprotective effect of dexamethasone, mediated through microglial inhibition, highlights microglia as an important therapeutic target for eosinophilic CRS-OD.