中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2026, Vol. 21 ›› Issue (8): 3598-3608.doi: 10.4103/NRR.NRR-D-24-01189

• 原著:脑损伤修复保护与再生 • 上一篇    下一篇

间歇性θ波刺激可促进促进缺血性脑卒中神经血管单位重塑

  

  • 出版日期:2026-08-18 发布日期:2026-04-27

Intermittent theta-burst stimulation promotes neurovascular unit remodeling after ischemic stroke in a mouse model

Jingjun Zhang1, 2, #, Ming Ding1, 3, #, Lu Luo1, Dan Huang1, Siyue Li1, Shuying Chen4, Yunhui Fan1, Li Liu1, Hongyu Xie1, Gang Liu1, Kewei Yu1, Junfa Wu1, Xiao Xiao3, *, Yi Wu1, *   

  1. 1Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China; 
    2Department of Rehabilitation Medicine, The Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; 
    3Behavioral and Cognitive Neuroscience Center, Institute of Science and Technology for Brain-Inspired Intelligence, Fudan University, Shanghai, China; 
    4Department of Laboratory Medicine, Huashan Hospital, Fudan University, Shanghai, China
  • Online:2026-08-18 Published:2026-04-27
  • Contact: Yi Wu, PhD, wuyi@fudan.edu.cn; Xiao Xiao, PhD, xiaoxiao@fudan.edu.cn.
  • Supported by:
    This study was supported by the National Key R&D Program of China, Nos. 2021ZD0202805 (to XX), 2019YFA0709504 (to XX); the National Natural Science Foundation of China, Nos. 82172544 (to YW), 32471083 (to XX), 81972140 (to JW), 82272604 (to HX), 82102491 (to SC); the Brain Science and Brain- Like Research Project of Shanghai Sixth People’s Hospital, No. ynnkxyb202410 (to JZ); and Shanghai Science and Technology Committee Sailing Program, No. 23YF1403800 (to LL).

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摘要：

神经血管单位在维持大脑结构、功能和稳态方面起着至关重要的作用。缺血性脑卒中后，神经血管单元的功能障碍和失调可导致神经血管解耦。间歇性θ波刺激是一种在θ波范围刺激的重复经颅磁刺激，可通过促进或抑制皮质兴奋性来调节皮质兴奋性。既往研究显示间歇性θ波刺激具有神经保护作用，但其作用机制尚不明确。实验对大脑中动脉闭塞再灌注构建的缺血性脑卒中小鼠模型进行间歇性θ波刺激干预。结果显示，间歇性θ波刺激可改善缺血性脑卒中模型小鼠的神经和运动功能，减少梗死半暗带中细胞的凋亡，激活PI3K/AKT/GSK3β/β-catenin信号通路。此外，间歇性θ波刺激还可通过PI3K/AKT/GSK3β和NF-κB通路抑制炎症，增强血脑屏障的完整性，并调节小胶质细胞和星形胶质细胞的极化。值得注意的是，间歇性θ波刺激能增强A2星形胶质细胞-血管偶联；且PI3K抑制剂LY294002可逆转间歇性θ波刺激的作用。上述结果表明，间歇性θ波刺激可通过PI3K/AKT/GSK3β和NF-κB信号通路调节小胶质细胞和星形胶质细胞，促进缺血性脑卒中的神经血管单位重塑，并改善功能预后。


https: //orcid.org/0000-0002-4955-3533 (Yi Wu); 

https: //orcid.org/0000-0002-4328-0634 (Xiao Xiao)

关键词: 缺血性脑卒中, 间歇性θ波刺激, 神经血管单位, 小胶质细胞, 星形胶质细胞, 神经炎症, 血脑屏障, 血管保护, 神经保护, 糖原合成酶激酶3β

Abstract: The neurovascular unit plays a critical role in maintaining brain structure, function, and homeostasis. Following ischemic stroke, dysfunction and dysregulation of this unit contribute to nerve–blood vessel uncoupling. Intermittent theta-burst stimulation is a repetitive transcranial magnetic stimulation that operates within the theta wave range and can either promote or inhibit cortical excitability. Previous studies have shown that intermittent theta wave stimulation has neuroprotective effects, but the underlying mechanisms remain unclear. In this study, mice subjected to middle cerebral artery occlusion/reperfusion were treated with intermittent theta-burst stimulation. The results showed that intermittent theta-burst stimulation significantly improved neurological function and motor recovery, reduced apoptosis in the peri-infarct region, and activated the PI3K/AKT/GSK3β/β-catenin signaling pathway. Additionally, intermittent theta-burst stimulation suppressed inflammation through the PI3K/AKT/GSK3β and NF-κB pathways. Notably, intermittent theta-burst stimulation strengthened A2 astrocyte–blood vessel coupling, and the effects of intermittent theta-burst stimulation were reversed by the PI3K inhibitor LY294002. These findings demonstrate that intermittent theta-burst stimulation promotes neurovascular unit remodeling and improves neurological outcomes by modulating microglia and astrocytes via the PI3K/AKT/GSK3β and NF-κB signaling pathways. 

Key words: astrocyte, blood–brain barrier, glycogen synthase kinase 3 beta, intermittent theta-burst stimulation, ischemic stroke, microglia, neural protection, neuroinflammation, neurovascular unit, vascular protection