Electroacupuncture Ameliorates Neuroinflammatory Damage and Cognitive Impairment in Vascular Dementia by Promoting Shh Signaling-Mediated Microglial M2 Polarization

Electroacupuncture (EA) has been documented to exert therapeutic benefits in vascular dementia (VD). This study seeks to elucidate the therapeutic efficacy and underlying molecular mechanisms of EA in VD. A VD model was induced in rats, which received EA with or without an Shh pathway inhibitor. An in vitro VD model was generated by exposing BV2 microglial cells to oxygen-glucose deprivation (OGD). A battery of tests was employed: cognitive function (novel object recognition and morris water maze), histopathology (H&E and TUNEL staining), synaptic ultrastructure (transmission electron microscope), microglial activation/polarization (immunofluorescence), inflammatory cytokine secretion (ELISA), protein expression (immunoblotting), and cellular viability (CCK-8). VD model rats exhibited attenuated Shh signaling in brain tissues, which was effectively restored by EA treatment in a duration-dependent manner. EA intervention observably improved cognitive performance, mitigated neuronal damage, enhanced synaptic plasticity, suppressed pro-inflammatory responses, and promoted microglial M2 polarization. These therapeutic effects were abolished by the Shh pathway inhibitor cyclopamine. Furthermore, Shh overexpression in microglia attenuated OGD-induced pro-inflammatory activation and reduced its detrimental impact on neuronal cells. Collectively, these data indicate that the cognitive benefits of EA in VD are critically dependent on Shh-driven reprogramming of microglial responses, which in turn resolves neuroinflammation and mitigates neuronal injury, thereby informing future therapeutic strategies.