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

作者：Jingjun Zhang, Ming Ding, Lu Luo, Dan Huang, Siyue Li, Shuying Chen, Yunhui Fan, Li Liu, Hongyu Xie, Gang Liu, Kewei Yu, Junfa Wu, Xiao Xiao, Yi Wu · 发表于：Neural Regeneration Research · 年份：2025 · DOI：10.4103/nrr.nrr-d-24-01189 · 被引用次数：10 · 研究领域：Transcranial Magnetic Stimulation Studies、Neuroinflammation and Neurodegeneration Mechanisms、Neuroscience and Neuropharmacology Research

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.