tDCS ameliorates CUMS-induced neuroinflammation and fasciitis by mediating microglial M1/M2 polarization.

Chronic unpredictable mild stress (CUMS) induces depression-like behaviors and may exacerbate pain perception through neuroinflammatory mechanisms, in which microglial polarization plays a crucial role. However, its effects on fascial tissues remain unclear. This study aimed to investigate the regulatory effects of transcranial direct current stimulation (tDCS) on neuroinflammation and structural/functional alterations of lumbar fascia in CUMS-induced rats, with particular focus on microglial involvement. An 8-week CUMS depression model was established in Sprague-Dawley (SD) rats, followed by tDCS intervention. Comprehensive assessments were performed using behavioral tests, ultrasonography, hematoxylin-eosin (H&E) staining, Masson staining, immunohistochemistry (IHC), and Western blot (WB) to evaluate depression-like behaviors, neuronal damage, fascial morphology, and inflammatory protein expression. Results demonstrated that CUMS rats exhibited significant depression-like behaviors, neuronal injury, and neuroinflammatory responses, accompanied by fibrosis, thickening, and inflammatory infiltration in the lumbar fascia. Immunological analysis revealed enhanced M1 microglial activation with concurrent suppression of M2 polarization in the CUMS group. Following tDCS intervention, rats showed marked improvements in depression-like behaviors, reduced neuronal damage, attenuated fascial fibrosis and inflammation, as well as decreased fascial thickening and edema on ultrasonography. The enhanced hindlimb weight-bearing capacity suggested alleviation of low back pain. Mechanistic studies indicated that tDCS effectively suppressed M1 microglial activation while promoting M2 polarization. These findings suggest that the therapeutic effects of tDCS on CUMS-induced depressive-like behaviors may involve modulation of microglial polarization and attenuation of neuroinflammatory and fascial inflammatory responses.