Byline: Bing-Qian. Cao, Feng. Tan, Jie. Zhan, Peng-Hui. Lai
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.
Stroke is the second leading cause of death worldwide, and it is a primary cause of death and disability, thus endangering human health (Feigin and Brainin, 2019). The ischemic penumbra can be spared by restoring blood perfusion. At present, the most effective treatments are thrombolysis and interventional therapy, but both of these treatments have a limited time window. Therefore, an alternative treatment strategy for cerebral ischemia/reperfusion (CI/R) injury is urgently needed to promote recovery of neurological function through multiple targets using multi-directional comprehensive treatments and alleviate the burden of stroke on society and the family. The pathological mechanism of CI/R is complex. Energy metabolism disorders, excitatory amino acid toxicity, inflammatory reactions, penumbra depolarization, and apoptosis are involved in the pathophysiological process (George and Steinberg, 2015). The cytokine-mediated inflammatory response plays a crucial role in the pathological injury of CI/R (Kawabori and Yenari, 2015). Many animal studies have found that damage-associated molecular patterns (DAMPs) recognize the widely expressed Toll-like receptors (TLRs), endogenous cannabinoid system receptors, and Notch receptors on microglia, perivascular macrophages, and vascular endothelial cells and activate multiple inflammatory signaling pathways. On the one hand, DAMPs activate the innate immune system, which prevents immune cells from producing anti-inflammatory factors, clears dead cells and extracellular matrix fragments in infarcted areas, and alleviates inflammatory responses. On the other hand, the resulting dynamic ion imbalance and brain dysfunction causes an excessive increase in inflammatory cell chemotaxis, adhesion, and infiltration of damaged brain tissue, resulting in the production of pro-inflammatory factors. Subsequently, these inflammatory factors increase inflammatory cell infiltration, resulting in further release of inflammatory mediators and reactive oxygen species, triggering an inflammatory cascade reaction....