TLR4 and major depressive disorder: reported that 2% sevoflurane exposure alleviated depressive-like behavior in a CUMS model by modulating the HMGB1-TLR4 pathway (190), In addition, a clinical case series described significant improvement in a patient with refractory depression following low-dose sevoflurane treatment (191).These findings suggest that sevoflurane may represent a promising adjunctive or alternative therapeutic strategy for depression.