Zhang Jingjun, Li Siyue, Huang Dan, Fu Jiale, Chen Shuying, Ren Na, Yang Pengkun, Song Di, Bai Xiaochen, Xie Hongyu, Liu Gang, Yu Kewei, Ng Shamay S M, Wu Junfa, Xiao Xiao, Wu Yi
Department of Rehabilitation Medicine, The Sixth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Rehabilitation Medicine, Huashan Hospital, Fudan University, 12 Wulumuqi Middle Road, Shanghai, 200040, China.
Mol Brain. 2025 Jun 9;18(1):48. doi: 10.1186/s13041-025-01222-w.
Secondary injuries from ischemia‒reperfusion in stroke, such as edema and hemorrhagic transformation, can significantly impact brain function. This study investigated the effects of intermittent theta burst stimulation (iTBS) on neurological function and cerebral blood flow in a mouse model of ischemia‒reperfusion injury. Laser speckle flowmetry was used to assess changes in cortical blood flow before and after ischemia‒reperfusion. Behavioral assessments were conducted to evaluate motor function recovery. The impact of iTBS on neuronal damage and apoptosis in the peri-infarct area was evaluated via Nissl staining and a TUNEL assay. RNA transcriptome sequencing and immunofluorescence staining were performed to investigate the effects of iTBS on microglial and astrocyte activation and the associated inflammatory response. Our findings demonstrated that iTBS significantly mitigated abnormal perfusion in the infarcted hemisphere, reduced neuronal damage and apoptosis in the peri-infarct area, and enhanced motor function in ischemic mice. Furthermore, iTBS promoted the polarization of microglia and astrocytes toward the anti-inflammatory M2 and A2 phenotypes. Therefore, iTBS provides neurovascular protection by modulating microglial and astrocyte activation and regulating the inflammatory response in the peri-infarct area, thereby improving abnormal cerebral blood flow in both the acute and subacute phases after ischemic brain injury.
中风中缺血再灌注引起的继发性损伤，如水肿和出血性转化，会对脑功能产生重大影响。本研究调查了间歇性θ波爆发刺激（iTBS）对缺血再灌注损伤小鼠模型神经功能和脑血流的影响。使用激光散斑血流仪评估缺血再灌注前后皮质血流的变化。进行行为评估以评价运动功能恢复情况。通过尼氏染色和TUNEL检测评估iTBS对梗死灶周围区域神经元损伤和凋亡的影响。进行RNA转录组测序和免疫荧光染色，以研究iTBS对小胶质细胞和星形胶质细胞活化及相关炎症反应的影响。我们的研究结果表明，iTBS显著减轻了梗死半球的异常灌注，减少了梗死灶周围区域的神经元损伤和凋亡，并增强了缺血小鼠的运动功能。此外，iTBS促进小胶质细胞和星形胶质细胞向抗炎性M2和A2表型极化。因此，iTBS通过调节小胶质细胞和星形胶质细胞活化以及梗死灶周围区域的炎症反应来提供神经血管保护，从而改善缺血性脑损伤后急性期和亚急性期的异常脑血流。
