Electroacupuncture promotes microglial M2 polarization in ischemic stroke via annexin A1

• Published in: Acupuncture in medicine : journal of the British Medical Acupuncture Society 2022-06, Vol.40 (3), p.258-267
• Main Authors: Zou, Jing, Huang, Guo-fu, Xia, Qian, Li, Xing, Shi, Jing, Sun, Ning
• Format: Article
• Language: English
• Subjects: Animals; Annexin A1 - genetics; Annexin A1 - metabolism; Brain Ischemia - genetics; Brain Ischemia - metabolism; Brain Ischemia - therapy; Cytokines; Cytokines - metabolism; Disease Models, Animal; Electroacupuncture; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - therapy; Ischemia; Ischemic Stroke - therapy; Mice; Microglia; Nitric oxide; Stroke; Stroke - metabolism; Tumor Necrosis Factor-alpha - metabolism; Tumor necrosis factor-TNF
• ISSN: 0964-5284; 1759-9873
• DOI: 10.1177/09645284211057570

Background: Neuroinflammation is the leading cause of neurological sequelae in ischemic stroke. Recently, we reported that the anti-inflammatory mediator annexin A1 (ANXA1) favored microglial M2 polarization in brain injury. The purpose of this study was to investigate electroacupuncture (EA) treatment and its potentially ANXA1-mediated anti-inflammatory effects in the middle cerebral artery occlusion/reperfusion (MCAO/R) mouse model of stroke. Methods: Treatment with EA consisted of dense-sparse frequencies (alternating 4 Hz sparse waves for 1.5 s and 16 Hz dense waves for 1.5 s) at CV24 and GV26. Intracerebroventricular (ICV) injection of Boc-2 (5 µM) or short hairpin RNA (sh)ANXA1 (2 µL) 3 days before EA was performed to block the effects of ANXA1. Results: EA pretreatment enhanced expression of ANXA1 and its receptor, formyl peptide receptor (FPR), when compared to MCAO/R alone. EA treatment also rescued MCAO/R-induced deficits in neurological performance, and learning and memory, and reduced infarct volume. Double immunofluorescent labeling showed that EA prevented MCAO/R-induced changes in microglial activation and morphology. EA also reduced the release of pro-inflammatory cytokines, such as interleukin (IL)-1β, inducible nitric oxide synthase (iNOS) and tumor necrosis factor (TNF)-α, while increasing the release of anti-inflammatory cytokines, such as arginase-1 (Arg-1) and brain-derived neurotrophic factor (BDNF). All EA-induced effects were either partially or completely prevented by prior administration of FPR antagonist Boc-2 or shANXA1. Conclusion: The current study provides strong evidence that EA treatment has protective effects against ischemic stroke in the MCAO/R mouse model and that the mechanism likely involves the promotion of M2 polarization in microglia via ANXA1.