Mechanism underlying treatment of ischemic stroke using acupuncture: transmission and regulation

Abstract

The inflammatory response after cerebral ischemia/reperfusion is an important cause of neurological damage and repair. After cerebral ischemia/reperfusion, microglia are activated, and a large number of circulating inflammatory cells infiltrate the affected area. This leads to the secretion of inflammatory mediators and an inflammatory cascade that eventually causes secondary brain damage, including neuron necrosis, blood-brain barrier destruction, cerebral edema, and an oxidative stress response. Activation of inflammatory signaling pathways plays a key role in the pathological process of ischemic stroke. Increasing evidence suggests that acupuncture can reduce the inflammatory response after cerebral ischemia/reperfusion and promote repair of the injured nervous system. Acupuncture can not only inhibit the activation and infiltration of inflammatory cells, but can also regulate the expression of inflammation-related cytokines, balance the effects of pro-inflammatory and anti-inflammatory factors, and interfere with inflammatory signaling pathways. Therefore, it is important to study the transmission and regulatory mechanism of inflammatory signaling pathways after acupuncture treatment for cerebral ischemia/reperfusion injury to provide a theoretical basis for clinical treatment of this type of injury using acupuncture. Our review summarizes the overall conditions of inflammatory cells, mediators, and pathways after cerebral ischemia/reperfusion, and discusses the possible synergistic intervention of acupuncture in the inflammatory signaling pathway network to provide a foundation to explore the multiple molecular mechanisms by which acupuncture promotes nerve function restoration.

Keywords: acupuncture; central nervous system; factor; inflammation; ischemic stroke; pathways; protein; stroke.

Figure 1

Inflammatory signal transmission related to acupuncture interventions after CI/R. ⊕ Indicates that acupuncture can promote and up-regulate pathways or the release of inflammatory mediators. ⊖ Indicates that acupuncture inhibits pathways or down-regulates the release of inflammatory mediators. ⊕/⊖ Indicates that acupuncture may exert biphasic regulation. For example, in the early stage of ischemia, acupuncture can up-regulate expression of the TLR4/NF-κB pathway, promote the proliferation and differentiation of glial cells and early scar formation, provide nutritional protection, and limit the inflammatory response. In the late stage, the TLR4/NF-κB pathway and TNF-α, IL-1β, IL-6, and other inflammatory cytokines are inhibited, which significantly improves nerve injury and reduces the inflammatory response. Acupuncture also exerts biphasic regulatory effects on microglia, which not only increases the phagocytic function of microglia in the ischemic penumbra, but also downregulates the inflammatory damage caused by the over activation of microglia. ACTH: Adreno-corticotropic hormone; BDNF: brain-derived neurotrophic factor; CB2: type II cannabinoid receptor; CI/R: cerebral infarction/reperfusion; DAMP: damage-associated molecular pattern; eNSC: endogenous neural stem cell; ERK: extracellular regulated protein kinase; ICAM-1: intercellular cell adhesion molecule-1; IFN-γ: interferon-γ; IGF-1: insulin-like growth factor-1; IL: interleukin; JAK2: Janus kinase 2; JNK: c-jun N-terminal kinase; MCPIP: monocyte chemotactic protein-induced protein; MMP: matrix metalloproteinase; NF-κB: nuclear factor kappa-B; NOS: nitric oxide synthase; P2X7R: P2X purinoceptor 7; P2Y1R: P2Y purinoceptor 1; P2Y7R: P2Y purinoceptor 7; PGE2: prostaglandin E2; PI3K: phosphatidylinositol 3-kinase; SOCS-3: suppressor of cytokine signaling 3; STAT3: signal transducer and activator of transcription 3; TGF-β: transforming growth factor-β; TLR4: Toll like receptor 4; TNF-α: tumor necrosis factor-α; TREM2: triggering receptor expressed on myeloid cells 2; VEC: vascular endothelial cell; α7nAChR: α7 nicotinic acetylcholine receptor.