A major side effect of reperfusion therapy following myocardial infarction is myocardial ischemia-reperfusion injury (MIRI). Electroacupuncture preconditioning (EA-pre) has a long history in the treatment of cardiovascular diseases. Here, we demonstrate how EA-pre attenuates MIRI by affecting the phagocytosis of neuronal dendritic spines of microglia of the fastigial nucleus (FN^microglia). We observed that EA-pre increased activity in FN^GABA and then improved myocardial injury by inhibiting abnormal activities of glutaminergic neurons of the FN (FN^Glu) during MIRI. Interestingly, we observed changes in the quantity and shape of FN microglia in mice treated with EA-pre and a decrease in the phagocytosis of FN^GABA neuronal dendritic spines by microglia. Furthermore, the effects of improving MIRI were reversed when EA-pre mice were chemically activated by intra-FN lipopolysaccharide injection. Overall, our results provide new insight indicating that EA-pre regulates microglial engulfment capacity, thus promoting the improvement of cardiac sympathetic nervous disorder during MIRI.

Background: Myocardial ischemia–reperfusion can further exacerbate myocardial injury and increase the risk of death. Our previous research found that the paraventricular nucleus (PVN) of the hypothalamus plays a crucial role in the improvement of myocardial ischemia–reperfusion injury (MIRI) by electroacupuncture (EA) pretreatment, but its mechanism of action is still unclear. CRH neurons exhibit periodic concentrated expression in PVN, but further research is needed to determine whether they are involved in the improvement of MIRI by EA pretreatment. Meanwhile, numerous studies have shown that changes in sympathetic nervous system innervation and activity are associated with many heart diseases. This study aims to investigate whether EA pretreatment improves MIRI through sympathetic nervous system mediated by PVN^CRHneurons.Methods: Integrated use of fiber-optic recording, chemical genetics and other methods to detect relevant indicators: ECG signals were acquired through Powerlab standard II leads, and LabChart 8 calculated heart rate, ST-segment offset, and heart rate variability (HRV); Left ventricular ejection fraction (LVEF), left ventricular short-axis shortening (LVFS), left ventricular end-systolic internal diameter (LVIDs) and interventricular septal thickness (IVSs) were measured by echocardiography; Myocardial infarct area (IA) and area at risk (AAR) were calculated by Evans-TTC staining. Pathological changes in cardiomyocytes were observed by HE staining; Changes in PVN^CRHneuronal activity were recorded by fiber-optic photometry; Sympathetic nerve discharges were recorded for in vivo electrophysiology; NE and TH protein expression was assayed by Western blot.Results: Our data indicated that EA pretreatment can effectively alleviate MIRI. Meanwhile, we found that in the MIRI model, the number and activity of CRH neurons co labeled with c-Fos in the PVN area of the rat brain increased, and the frequency of sympathetic nerve discharge increased. EA pretreatment could reverse this change. In addition, the results of chemical genetics indicated that inhibiting PVN^CRHneurons has a similar protective effect on MIRI as EA pretreatment, and the activation of PVN^CRHneurons can counteract this protective effect.Conclusion: EA pretreatment can inhibit PVN^CRHneurons and improve MIRI by inhibiting sympathetic nerve, which offers fresh perspectives on the application of acupuncture in the management of cardiovascular disease.

Cardiovascular disease is the leading cause of death worldwide. As a traditional Chinese treatment method, acupuncture has a unique role in restoring the balance of the human body environment. Due to its safety, non-invasive nature, and effectiveness in treating cardiovascular diseases, acupuncture has been widely welcomed and recognized among the world. A large amount of evidence shows that acupuncture can effectively regulate cardiovascular diseases through the autonomic nervous system. The hypothalamus, as an important component of regulating the autonomic nervous system, plays an important role in regulating the internal environment, maintaining homeostasis, and preserving physiological balance. However, there is currently a scarcity of review articles on acupuncture signal transduction and acupuncture improving cardiovascular disease through the hypothalamus and autonomic nervous system. This review delves into the transduction of acupuncture signals and their neural regulatory mechanisms on the hypothalamus and autonomic nervous system, elucidating their impact on cardiovascular disease. Review the basic and clinical studies on acupuncture signal transduction mechanisms and the role of the hypothalamus and ANS in acupuncture treatment of cardiovascular diseases published in four English databases (PubMed, Web of Science, MEDLINE, and Springer Cochrane Library) and two Chinese databases (Wanfang Database and China National Knowledge Infrastructure Database) over the past 20 years. Through sensory stimulation, acupuncture effectively transmits signals from the periphery to the hypothalamus, where they are integrated, and finally regulate the autonomic nervous system to treat cardiovascular diseases. Acupuncture exhibits significant potential as a therapeutic modality for cardiovascular diseases by orchestrating autonomic nervous system regulation via the hypothalamus, thereby gifting novel perspectives and methodologies for the prevention and treatment of cardiovascular ailments.

This study demonstrates that EA preconditioning can attenuate myocardial injury for MIRI, which is similar to inhibition of glutamatergic neurons in LH. However, chemical activation of glutamatergic neurons in LH attenuates the protective effect of EA pretreatment. These findings help better understand the mechanisms of EA to regulate cardiac function.