Electroacupuncture Ameliorates Cognitive Impairment in Vascular Dementia Rats: Potential Involvement of the Astrocyte–Synapse Axis

INTRODUCTION: This study investigated whether electroacupuncture at "Zhisanzhen" (EA-ZSZ) alleviates cognitive impairment in vascular dementia (VD) rats by regulating the astrocyte-synapse axis, reshaping the hippocampal secretory microenvironment, and preserving synaptic structural integrity. METHODS: Sprague-Dawley rats were divided into sham, VD, VD+EA, and VD+Nim (nimodipine) groups. The VD model was established via a modified bilateral common carotid artery occlusion (2-VO). After 21 days, learning and memory were evaluated using the Morris water maze. Hippocampal CA1 histopathology and ultrastructure were assessed by H&E and transmission electron microscopy (TEM). RNA-seq identified differentially expressed genes (DEGs) and pathways. GFAP, BDNF, bFGF, and cytokines (IL-1β, IL-6, and TNF-α) were measured via immunofluorescence, Western blot, and ELISA. RESULTS: Compared to sham group, VD rats exhibited cognitive impairment, neuronal disorganization, and synaptic disruption. EA-ZSZ markedly alleviated cognitive deficits, outperforming nimodipine in spatial learning/memory, and restored synaptic ultrastructure (showing clearer clefts and increased vesicle abundance on TEM). RNA-seq showed that EA-ZSZ normalized pathways associated with cytokine-cytokine receptor interactions and synaptic signaling, restoring key "reversal genes" (Mdk, Homer1, and Npas4). These changes were accompanied by reduced GFAP, upregulated hippocampal BDNF/bFGF, and suppressed systemic cytokines (IL-1β, IL-6, and TNF-α). CONCLUSION: EA-ZSZ exerts significant neuroprotective effects in VD rats by modulating the astrocyte-synapse axis, suppressing neuroinflammation, and enhancing neurotrophic/structural support within the hippocampal microenvironment. This highlights its multi-target advantage over monotherapies in repairing damaged synaptic architecture, supporting its clinical use.