The State Key Laboratory of Bioelectronics, Jiangsu Key Laboratory of Biomaterials and Devices, School of Biological Science and Medical Engineering, Southeast University, Nanjing, 210009, P. R. China.
Section of Pacing and Electrophysiology, Division of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210009, P. R. China.
Nanoscale. 2023 Feb 16;15(7):3532-3541. doi: 10.1039/d2nr05073k.
The imbalance between the sympathetic and the parasympathetic nervous system is one of the main pathogeneses of myocardial infarction (MI). Vagus nerve stimulation (VNS), which restores autonomic nervous balance by enhancing the parasympathetic drive, is shown to have benefits for patients with MI. As a clinically safe and effective remote neuromodulation method, magnetic stimulation is expected to overcome the problems of infection and nerve injury caused by electrode implantation. However, it is difficult to achieve precise stimulation on a single vagus nerve due to the poor focus of the magnetic field. Here, we described a novel magnetic vagus nerve stimulation (mVNS) system, which consisted of an injectable chitosan/β-glycerophosphate (CS/GP) hydrogel loaded with superparamagnetic iron oxide (SPIO) nanoparticles and a mild magnetic pulse sequence. The injectable hydrogel prepared from clinically safe materials ensured minimally invasive implantation, and the SPIO nanoparticles in the hydrogel mediated the precise magnetic stimulation of a single vagus nerve. Under a mild magnetic field (∼100 mT), a decrease in heart rate and a change in vagus nerve potential were found in rats under injection of a magnetic CS/GP hydrogel. Magnetic stimulation on the vagus nerve for 4 weeks (20 Hz, three times daily, 5 minutes each time) significantly improved the cardiac function and reduced the infarct size of the rats subjected to myocardial infarction, accompanied by suppression of inflammatory cell infiltration and inflammation factor expression. Taken together, these results demonstrated that the mVNS exhibited promising potential for treating myocardial infarction in the clinic.
交感神经和副交感神经系统失衡是心肌梗死 (MI) 的主要发病机制之一。迷走神经刺激 (VNS) 通过增强副交感神经驱动来恢复自主神经平衡，已被证明对 MI 患者有益。作为一种临床安全有效的远程神经调节方法，磁场刺激有望克服因电极植入而引起的感染和神经损伤问题。然而，由于磁场的聚焦性差，很难对单一迷走神经进行精确刺激。在这里，我们描述了一种新型的磁刺激迷走神经（mVNS）系统，它由一种可注射的壳聚糖/β-甘油磷酸酯（CS/GP）水凝胶和超顺磁性氧化铁（SPIO）纳米粒子组成，并采用了温和的磁场脉冲序列。这种由临床安全材料制备的可注射水凝胶确保了微创植入，并且水凝胶中的 SPIO 纳米粒子介导了对单一迷走神经的精确磁刺激。在温和磁场（约 100 mT）下，在向大鼠注射磁 CS/GP 水凝胶后，心率降低和迷走神经电位发生变化。对迷走神经进行 4 周的磁刺激（20 Hz，每日 3 次，每次 5 分钟）显著改善了心肌梗死大鼠的心脏功能并减小了梗死面积，同时抑制了炎症细胞浸润和炎症因子的表达。总之，这些结果表明 mVNS 在临床上治疗心肌梗死具有很大的潜力。
