2. Academic Validation
  3. Mechanistic insights into the neuroprotective effects of low-intensity transcranial ultrasound stimulation in post-cardiac arrest brain injury: Modulation of the Piezo1-Dkk3/PI3K-Akt pathway

Mechanistic insights into the neuroprotective effects of low-intensity transcranial ultrasound stimulation in post-cardiac arrest brain injury: Modulation of the Piezo1-Dkk3/PI3K-Akt pathway

  • Brain Behav Immun. 2025 Jul:127:341-357. doi: 10.1016/j.bbi.2025.03.027.
Shuang Xu 1,  Lulu Gu 2,  Banghe Bao 3,  Qian Liu 2,  Qiaofeng Jin 4,  Yannan Ma 5,  Siyi Zhou 2,  Beibei Li 2,  Li Xu 2,  Guangqi Guo 6,  Jinpiao Zhu 7,  Kuan-Pin Su 8,  Peng Sun 9
Affiliations

Affiliations

  • 1 Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, China; Department of Critical Care Medicine, Henan Key Laboratory for Critical Care Medicine, Zhengzhou Key Laboratory for Critical Care Medicine, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Henan University People's Hospital, Zhengzhou, China.
  • 2 Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, China.
  • 3 Department of General Surgery, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, China.
  • 4 Department of Ultrasound Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • 5 Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Department of Emergency Medicine, Beijing Chao-Yang Hospital Capital Medical University, Beijing, China.
  • 6 Sun Yat-sen University Cancer Center, Guangzhou, China.
  • 7 Department of Rehabilitation, Perioperative and Systems Medicine Laboratory, The Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, China. Electronic address: zhujinpiao@zju.edu.cn.
  • 8 Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan; College of Medicine, China Medical University, Taichung, Taiwan; An-Nan Hospital, China Medical University, Tainan, Taiwan. Electronic address: cobol@cmu.edu.tw.
  • 9 Department of Emergency Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, China. Electronic address: sp761397@sina.com.
PMID: 40118226 DOI: 10.1016/j.bbi.2025.03.027
Abstract

Post-cardiac arrest brain injury (PCABI) remains a significant challenge, marked by high mortality and disability rates due to persistent neuroinflammation. This study explored the neuroprotective potential of low-intensity transcranial ultrasound stimulation (LITUS) in mitigating brain damage after cardiopulmonary resuscitation (CPR) using a murine model and in vitro assays. LITUS treatment improved 24-h survival rates and neurological recovery in cardiac arrest (CA) mice, as evidenced by behavioral assessments and reduced neurological deficit scores. Proteomic analyses revealed modulation of Piezo1-Dkk3/PI3K-Akt signaling pathway, characterized by decreased pro-inflammatory cytokines (IL-1β, IL-6, TNF-α). Mechanistic studies demonstrated that LITUS enhanced Piezo1 and Dkk3 activation, promoting calcium influx and anti-inflammatory responses. The Piezo1 antagonist GsMTx4 abrogated these effects, underscoring Piezo1's specific role. Additionally, in vitro experiments using oxygen/glucose deprivation and reoxygenation (OGD/R)-treated BV2 microglial cells confirmed that LITUS reduced inflammatory responses and enhanced cellular recovery via the Piezo1-Dkk3 axis. These findings highlight LITUS as a promising non-invasive therapeutic strategy to ameliorate PCABI by modulating neuroinflammation through the Piezo1-Dkk3/PI3K-Akt pathway. This work provides a basis for translational research and potential clinical applications in improving outcomes for CPR survivors.

Keywords

Brain injury; Cardiopulmonary resuscitation; Inflammation; Piezo1; Ultrasound stimulation.

Figures
Products
Inhibitors & Agonists
Other Products