Long-term transcranial ultrasound stimulation regulates neuroinflammation to ameliorate post–myocardial infarction cardiac arrhythmia and remodeling
Haoyuan Hu, Huijun Wu, Tongjian Zhu, Ye Cheng, Wei Guo, Tuantuan Tan, Changhao Hu, Hong Jiang, Songyun Wang
Heart Rhythm 2025 · 10.1016/j.hrthm.2024.10.017
Abstract
Background Sympathetic overactivation and neuroinflammation in the paraventricular nucleus (PVN) are crucial factors in post-myocardial infarction (MI) cardiac remodeling and ventricular arrhythmias (VAs). Prior study has indicated that low-intensity focused ultrasound stimulation could attenuate sympathetic neuroinflammation within the PVN to prevent the occurrence of VAs in an acute MI model. Meanwhile, the cGAS-STING pathway has shown potential to ameliorate the neuroinflammatory response. However, the effect and mechanisms of long-term transcranial ultrasound stimulation (LTUS) for modulating neuroinflammation in the chronic stage of MI remain unclear. Objective This study aimed to ascertain whether LTUS could mitigate post-MI neuroinflammation and improve cardiac arrhythmia and remodeling through the cGAS-STING pathway. Methods Thirty-six SD rats were equally randomized to the sham group (pseudo-MI modeling), chronic MI group (MI modeling), and LTUS group (MI modeling and long-term ultrasound stimulation). Transcranial ultrasound stimulation (15 min/d) was conducted on the PVN for 4 consecutive weeks. After 4-week intervention, echocardiography, electrophysiologic experiments, and histopathologic staining were performed to assess the role of LTUS on post-MI neuroinflammation and cardiac remodeling. Results The results indicated that LTUS significantly facilitated microglial M1 to M2 polarization through the cGAS-STING signaling pathway within the PVN. Furthermore, LTUS inhibited MI-induced sympathetic neuroinflammation, thereby improving cardiac dysfunction, ameliorating cardiac remodeling, and reducing VA inducibility. Conclusion Long-term ultrasound stimulation of the PVN was found to alleviate post-MI neuroinflammation and to improve cardiac remodeling, which might inspire novel insights and clinical strategies for noninvasive neuromodulation and the treatment of post-MI VAs.
Abstract via europepmc.
Exposures
Exposure 1: LTUS to the PVN, daily for 4 weeks
Target: paraventricular nucleus — “paraventricular nucleus (PVN)”
Device: other named manufacturer · Haobro Medical Device Co, Ltd, Soochow, China · HB810B ✓
| Waveform | not reported | |
|---|---|---|
| Fundamental frequency (kHz) | not reported | ⚑ |
| Pulse duration (ms) | not reported | |
| Pulse repetition frequency (Hz) | not reported | |
| Duty cycle (%) | not reported | |
| Sonication duration (s) | 900 | ✓✓✓⚑ |
| Free-field pressure (kPa) | not reported | |
|---|---|---|
| Free-field Isppa (W/cm²) | not reported | |
| Free-field Ispta (W/cm²) | not reported | |
| In-situ estimate | not reported | |
| In-situ pressure (kPa) | not reported | |
| In-situ Isppa (W/cm²) | not reported | |
| In-situ Ispta (W/cm²) | not reported |
The cranial surface covering the PVN region was irradiated for 15 minutes daily for 4 consecutive weeks after MI modelling. Acoustic parameters are in Supplemental Table S1, not in the main text.
Flags from extraction
exposures[0].timing.sonication_duration_s— 15 min per day is recorded as 900 s; this is the daily irradiation time, and whether it is one continuous train is not stated.n_subjects— 36 rats in three groups; only the LTUS group (n=12) received ultrasound. The text prints n = as 'n 5'.exposures[0].fundamental_frequency_khz— All acoustic parameters are in Supplemental Table S1, not in the main text.anaesthesia— Isoflurane stated for surgery; anaesthesia during stimulation is not stated.sham_type— The sham group is a pseudo-MI surgical sham and the CMI group is MI without ultrasound; the paper does not describe any sham ultrasound.