Chengdong Yang
Electroacupuncture at GV20 and ST36 was associated with reduced LPS-induced neuroinflammation and cognitive impairment and these changes were statistically consistent with involvement of the NLRP3-caspase-1-IL-1β/IL-18 pathway, with no significant sex differences. These findings suggest electroacupuncture may be a promising strategy for NLRP3-associated neuroinflammatory disorders.
OBJECTIVES: To determine the effect of electroacupuncture at GV20 (Baihui) and ST36 (Zusanli) in reducing the LPS-induced neuroinflammation and cognitive deficit. To determine whether it was associated with reduced activation of the NLRP3 inflammasome-caspase-1-IL-1β/IL-18 signaling pathway in both male and female rats.
PROCEDURES: Ninety-four adult Sprague-Dawley rats (47 male, 47 female) were randomly assigned to four groups: Control (saline), LPS (5 mg/kg intraperitoneal), LPS+EA (LPS plus electroacupuncture at GV20/ST36, 2 Hz, 1 mA, 20 min/day, 7 days), and LPS+Sham Electroacupuncture (LPS plus sham electroacupuncture at non-acupoints). Outcomes included NLRP3 and caspase-1 p20 (western blot), IL-1β, IL-18, IL-6, TNF-α, IL-10 (ELISA), ROS, MDA, GSH (oxidative stress assays), Iba-1, and GFAP (immunohistochemistry), GSDMD-NT, NeuN, NF-κB p65, phospho-NF-κB p65, BDNF, CD68, iNOS, Arginase-1, and cognitive function (Morris water maze, Y-maze, novel object recognition).
RESULTS: LPS increased all inflammatory and oxidative stress markers and impaired cognitive versus Controls (P < 0.001). Electroacupuncture was associated with significant reductions compared to LPS (P < 0.001): NLRP3 (48% reduction), caspase-1 p20 (54%), IL-1β (34%), IL-18 (33%), IL-6 (49%), TNF-α (49%), ROS (40%), MDA (47%), Iba-1 (46%), GFAP (47%), GSDMD-NT (54%), NF-κB p65 (46%), p-NF-κB p65 (68%), CD68 (57%), iNOS (68%), while increasing IL-10 (98%) and GSH (60%), NeuN (77%), BDNF (116%), Arginase-1 (500%), and improving cognition (21-133%). Sham EA had no effect on any outcome (P > 0.05 vs. LPS). No significant sex differences were detected. Mediation analysis revealed that 84.4% of electroacupuncture's cognitive benefit was mediated through the NLRP3-related pathways.
CONCLUSIONS: Electroacupuncture at GV20 and ST36 was associated with reduced LPS-induced neuroinflammation and cognitive impairment and these changes were statistically consistent with involvement of the NLRP3-caspase-1-IL-1β/IL-18 pathway, with no significant sex differences. These findings suggest electroacupuncture may be a promising strategy for NLRP3-associated neuroinflammatory disorders.