摘要Background:Vestibular migraine(VM)is a common disorder characterized by recurrent dizziness or vertigo,often aggravated by cold exposure.This study aimed to identify differentially expressed circular RNAs(circRNAs)in cold-region VM and explore the underlying molecular mechanisms.Methods:Peripheral blood samples from long-term residents of Heilongjiang Province profiled by circRNA microarray,and differentially expressed circRNAs were validated by quantitative reverse transcription polymerase chain reaction(qRT-PCR).A competing endogenous RNA(ceRNA)network and enriched pathways were inferred by bioinformatics.A VM-like mouse model was established using nitroglycerin(NTG)and kainic acid(KA)and confirmed by behavioral testing and western blot.The hsa_circ_0003201/miR-31-5p/triggering receptor expressed on myeloid cells 2(TREM2)axis and related pathways were examined in clinical samples and in the trigeminal nucleus caudalis(TNC)and vestibular nuclei(VN)of mice using qRT-PCR,enzyme-linked immunosorbent assay(ELISA),and western blot.CircRNA microarray profiling also compared expression patterns between VM and migraine patients.Results:Hsa_circ_0003201 was significantly upregulated in cold-region VM patients.Bioinformatic analyses revealed that hsa_circ_0003201 may regulate the miR-31-5p/TREM2 axis and be associated with phosphoinositide 3-kinase(PI3K)/protein kinase B(AKT)signaling,pyruvate metabolism,and transient receptor potential(TRP)pathways.Clinical validation confirmed increased hsa_circ_0003201 and TREM2 and decreased miR-31-5p.VM-like mice exhibited central sensitization and vestibular dysfunction,with increased TREM2,decreased miR-31-5p,and PI3K/AKT activation in the TNC and VN.Comparative circRNA analysis between VM and migraine patients indicated distinct expression patterns.Conclusion:Hsa_circ_0003201 shows potential as a diagnostic biomarker for cold-region VM,and the hsa_circ_0003201/miR-31-5p/TREM2 axis may contribute to pathogenesis through PI3K/AKT signaling,pyruvate metabolism,and TRP-related pathways.