Zhang Jingjun, Ding Ming, Luo Lu, Huang Dan, Li Siyue, Chen Shuying, Fan Yunhui, Liu Li, Xie Hongyu, Liu Gang, Yu Kewei, Wu Junfa, Xiao Xiao, Wu Yi
Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, Shanghai, China.
Department of Rehabilitation Medicine, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Neural Regen Res. 2025 Mar 25. doi: 10.4103/NRR.NRR-D-24-01189.
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.
神经血管单元在维持脑结构、功能和内环境稳定方面发挥着关键作用。缺血性中风后，该单元的功能障碍和失调会导致神经-血管解偶联。间歇性θ波爆发刺激是一种在θ波范围内运作的重复性经颅磁刺激，可促进或抑制皮质兴奋性。先前的研究表明，间歇性θ波刺激具有神经保护作用，但其潜在机制仍不清楚。在本研究中，对大脑中动脉闭塞/再灌注的小鼠进行间歇性θ波爆发刺激治疗。结果表明，间歇性θ波爆发刺激显著改善神经功能和运动恢复，减少梗死周围区域的细胞凋亡，并激活PI3K/AKT/GSK3β/β-连环蛋白信号通路。此外，间歇性θ波爆发刺激通过PI3K/AKT/GSK3β和NF-κB途径抑制炎症。值得注意的是，间歇性θ波爆发刺激增强了A2星形胶质细胞-血管耦合，并且PI3K抑制剂LY294002可逆转间歇性θ波爆发刺激的作用。这些发现表明，间歇性θ波爆发刺激通过PI3K/AKT/GSK3β和NF-κB信号通路调节小胶质细胞和星形胶质细胞，促进神经血管单元重塑并改善神经学结果。
