Neurochem Res. 2026 Jun 16;51(4):197. doi: 10.1007/s11064-026-04815-6.
ABSTRACT
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.
PMID:42301370 | DOI:10.1007/s11064-026-04815-6