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Electroacupuncture Pretreatment Alleviates Myocardial Ischemia-Reperfusion Injury by Inhibiting Engulfment
Xiang Zhou1,2, Peiyi Yang3, Chaonan Dong3
1College of Traditional Chinese Medicine, Anhui University of Chinese Medicine, Hefei, China.
Aim:
The occurrence of myocardial ischemia-reperfusion injury (MIRI) is accompanied by neuroinflammatory reactions and is closely related to the overactivation of microglia. Currently, effective clinical strategies to prevent MIRI are unclear. This study investigated potential therapeutic targets and the mechanisms of electroacupuncture pretreatment (EA-pre) for MIRI.
Methods:
A MIRI mouse model was established by ligating the left anterior descending branch of the heart for 30 min and reperfusion for 2 h. The mechanisms by which EA-pre alleviates MIRI were investigated through immunofluorescence staining, chemogenetics, and fiber photometry recordings, focusing on the potential involvement of microglia and glutamate (Glu) neurons in the lateral hypothalamic (LH).
Results:
EA-pre improves cardiac function in MIRI mice by suppressing microglial activation in the LH. The underlying mechanism likely involves EA-pre inhibition of microglial engulfment of inhibitory synapses around LHGlu neurons. Targeted activation of LHmicroglia reverses EA's inhibitory effect, thereby increasing LHGlu neuronal activity and triggering overactivation of the sympathetic nervous system (SNS), which ultimately exacerbates MIRI.
Conclusion:
EA-pre inhibits microglial engulfment of inhibitory synapses around LHGlu neurons in MIRI mice, thereby suppressing LHGlu neuronal activity, reducing SNS output, and ultimately exerting cardioprotective effects.
Insights
Electroacupuncture pretreatment (EA-pre) protects against myocardial ischemia-reperfusion injury (MIRI) by modulating microglia in the lateral hypothalamus. This treatment reduces neuroinflammation and sympathetic nervous system overactivation, offering a potential therapeutic strategy for MIRI.
Area of Science:
- Neuroscience
- Cardiology
- Immunology
Background:
- Myocardial ischemia-reperfusion injury (MIRI) involves neuroinflammation, particularly microglial activation.
- Current clinical strategies for preventing MIRI remain unclear.
- Microglia and glutamate (Glu) neurons in the lateral hypothalamus (LH) are implicated in MIRI pathogenesis.
Purpose of the Study:
- To investigate electroacupuncture pretreatment (EA-pre) as a therapeutic strategy for MIRI.
- To elucidate the underlying mechanisms of EA-pre in alleviating MIRI, focusing on LH microglia and Glu neurons.
- To identify potential therapeutic targets for MIRI prevention.
Main Methods:
- Establishment of a MIRI mouse model via coronary artery ligation and reperfusion.
- Immunofluorescence staining to assess microglial activation in the LH.
- Chemogenetics and fiber photometry recordings to investigate neuronal activity and microglial function.
- Analysis of synaptic changes and sympathetic nervous system (SNS) output.
Main Results:
- EA-pre significantly improved cardiac function in MIRI mice.
- EA-pre suppressed microglial activation and reduced the engulfment of inhibitory synapses around LH Glu neurons.
- Targeted activation of LH microglia reversed the protective effects of EA-pre, exacerbating MIRI via increased SNS activity.
Conclusions:
- EA-pre exerts cardioprotective effects against MIRI by inhibiting microglial activity in the LH.
- The mechanism involves preserving inhibitory synapses on LH Glu neurons, thereby reducing SNS overactivation.
- Modulating LH microglia represents a promising therapeutic approach for MIRI.
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