Objective:To investigate whether electroacupuncture (EA) alleviates cognitive impairment by suppressing the toll-like receptor 4 (rLR4)/myeloid differentiation factor 88 (MyD88) signaling pathway,which triggers immune-inflammatory responses in the hippocampus of rats with vascular dementia (VaD).Methods:The experiments were conducted in 3 parts and in total the Sprague-Dawley rats were randomly divided into 8 groups by a random number table,including sham,four-vessel occlusion (4-VO),4-VO+EA,4-VO+non-EA,sham+EA,4-VO+lipopolysaccharide (LPS),4-VO+LPS+EA,and 4-VO+TAK-242 groups.The VaD model was established by the 4-VO method.Seven days later,rats were treated with EA at 5 acupoints of Baihui (DV 20),Danzhong (RN 17),Geshu (BL 17),Qihai (RN 6) and Sanyinjiao (SP 6),once per day for 3 consecutive weeks.Lymphocyte subsets,lymphocyte transformation rates,and inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α) were measured to assess immune function and inflammation in VaD rats.Transmission electron microscopy was used to observe the ultrastructure of nerve cells in the hippocampus.The levels of TLR4,MyD88,IL-6,and TNF-α were detected after EA treatment.TLR4/MyD88 signaling and cognitive function were also assessed after intracerebroventricular injection of TLR4 antagonist TAK-242 or TLR4 agonist LPS with or without EA.Results:Compared with the 4-VO group,EA notably improved immune function of rats in the 4-VO+EA group,inhibited the protein and mRNA expressions of TLR4 and MyD88 in the hippocampus of rats,reduced the expressions of serum IL-6 and TNF-α (all P＜0.05 or P＜0.01),and led to neuronal repair in the hippocampus.There were no significant differences between the 4-VO+LPS+EA and 4-VO+EA groups,nor between the 4-VO+TAK-242 and 4-VO+EA groups (P＞0.05).Conclusions:EA attenuated cognitive impairment associated with immune inflammation by inhibition of the TLR4/MyD88 signaling pathway.Thus,EA may be a promising alternative therapy for the treatment of VaD.