PENG-based self-powered transcutaneous auricular vagus nerve stimulation attenuated myocardial infarction-induced heart-brain remodeling via ameliorating the neuroinflammatory response in central amygdala.

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.