基于PENG的自供电经皮耳迷走神经刺激通过改善中央杏仁核的神经炎症反应减轻心肌梗死诱导的心脏-脑重塑。
PENG-based self-powered transcutaneous auricular vagus nerve stimulation attenuated myocardial infarction-induced heart-brain remodeling via ameliorating the neuroinflammatory response in central amygdala.
作者信息
Xu Xiao, Qiao Jiaming, Wang Yuhong, Liu Zhihao, Liu Zihan, Tan Wuping, Wang Changyi, Peng Chen, Cheng Siyi, Han Xinrui, Wang Yueyi, Zhou Xiaoya, Zhang Yuanzheng, Zhou Liping, Jiang Hong
机构信息
Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Autonomic Nervous System Modulation, Wuhan 430060, China; Cardiac Autonomic Nervous System Research Center of Wuhan University, Wuhan 430060, China; Hubei Key Laboratory of Cardiology, Wuhan 430060, China; Cardiovascular Research Institute, Wuhan University, Wuhan 430060, China; Taikang Center for Life and Medical Sciences, Wuhan University, Wuhan 430060, China; Institute of Molecular Medicine, Renmin Hospital of Wuhan University, Wuhan 430060, China.
Department of Cardiology, Wuhan No.1 Hospital, Wuhan 430060, China.
出版信息
Int Immunopharmacol. 2025 Sep 23;162:115085. doi: 10.1016/j.intimp.2025.115085. Epub 2025 Jun 18.
BACKGROUND
Myocardial infarction (MI) is responsible for the majority of deaths worldwide and depression can intensify the detrimental cycle of heart-brain remodeling after MI. Transcutaneous auricular vagus nerve stimulation (taVNS) is an effective non-invasive neuromodulation strategy for treating depression and cardiovascular disease (CVD). Piezoelectric nanogenerators (PENGs) can convert the mechanical energy of organism into electrical energy to achieve self-powering. Self-powered vagal neuromodulation based on PENGs have been used for neural stimulation and CVD treatment. We aim to determine the interaction between heart and central amygdala (CeA), integrate self-powered PENG technology into taVNS system and explore the effects and underlying mechanisms of taVNS on heart-CeA remodeling after MI.
METHODS
Neural tracing and chemogenetic technologies were used to confirm the heart-CeA connectivity. A four-weeks taVNS treatment was promoted after MI induction in male Sprague-Dawley rats. Then, depression-like behaviors and cardiac remodeling were evaluated. Besides, neuronal activity and neuroinflammation levels were assessed and the underlying mechanisms were elucidated. The self-powered PENG technology was integrated into the taVNS system and its neuromodulation effectiveness was evaluated.
RESULTS
MI increased neuronal activity in the CeA and depression-like behaviors, and over-activation of the CeA led to cardiac dysfunction, resulting in malignant feedback. taVNS attenuated MI-induced "heart-CeA" remodeling, improved cardiac function, and reduced depression-like behaviors by ameliorating the neuroinflammatory response via MLCK pathway in the CeA. In addition, the self-powered PENG-based system enabled effective transcutaneous neuromodulation.
CONCLUSION
PENG-based self-powered taVNS holds potential for heart-brain neuromodulation, offering a synergistic strategy for treating cardiac and mental co-morbidities after MI.
背景
心肌梗死（MI）是全球大多数死亡的原因，而抑郁症会加剧心肌梗死后心脑重塑的有害循环。经皮耳迷走神经刺激（taVNS）是一种治疗抑郁症和心血管疾病（CVD）的有效非侵入性神经调节策略。压电纳米发电机（PENGs）可以将生物体的机械能转化为电能以实现自供电。基于PENGs的自供电迷走神经调节已用于神经刺激和心血管疾病治疗。我们旨在确定心脏与中央杏仁核（CeA）之间的相互作用，将自供电的PENG技术整合到taVNS系统中，并探索taVNS对心肌梗死后心脑重塑的影响及其潜在机制。
方法
采用神经示踪和化学遗传学技术来确认心脏与CeA之间的连接。在雄性Sprague-Dawley大鼠诱导心肌梗死后进行为期四周的taVNS治疗。然后，评估抑郁样行为和心脏重塑。此外，评估神经元活动和神经炎症水平并阐明其潜在机制。将自供电的PENG技术整合到taVNS系统中并评估其神经调节效果。
结果
心肌梗死增加了CeA中的神经元活动和抑郁样行为，而CeA的过度激活导致心脏功能障碍，从而产生恶性循环。taVNS减轻了心肌梗死诱导的“心-脑”重塑，改善了心脏功能，并通过改善CeA中MLCK途径的神经炎症反应减少了抑郁样行为。此外，基于PENG的自供电系统实现了有效的经皮神经调节。
结论
基于PENG的自供电taVNS在心脏-脑神经调节方面具有潜力，为治疗心肌梗死后的心脏和精神共病提供了一种协同策略。
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