Abstract Background and aims Stroke has become the third leading cause of death globally and the top one among Chinese residents, imposing heavy social and familial burdens. Ischemic stroke patients with acute large-vessel occlusion face higher mortality. Despite early endovascular therapy restoring blood supply and salvaging the ischemic penumbra, nearly half still fail to achieve functional independence, called futile recanalization. Transcranial magnetic stimulation is a promising physical therapy; its modality continuous theta-burst stimulation (cTBS) works well in stroke models, yet its benefits for futile recanalization remain unclear. We hypothesized cTBS improves glymphatic function in MCAO rat models to boost recovery. By establishing MCAO models and delivering cTBS, we will assess outcomes, analyze neurological/histological features and explore related mechanisms, laying a theoretical basis for clinical cTBS use in acute ischemic stroke. Methods Firstly, MCAO models were established; cTBS (neural plasticity-modulating stimulation) was initiated within 3 h post-modeling and delivered consecutively for 7 days. Secondly, assessments included behavioral tests (functional recovery scoring), histological analyses (e.g., TTC staining), and GS tracing (cerebrospinal fluid tracers for inflow/outflow). Thirdly, mechanistic experiments (dCLN ligation, AQP4 KO/TGN020) were conducted to verify cTBS’s GS-dependent effects. Results cTBS significantly reduced infarct volume (TTC staining), improved neurological function, and enhanced GS’s arterial inflow, venous outflow, and AQP4-mediated convection. dCLN ligation or AQP4 inhibition/knockout fully abolished cTBS’s protective effects. Conclusions cTBS alleviates MCAO injury by enhancing GS function (dependent on lymphatic drainage and AQP4), providing a mechanistic basis for cTBS in clinical acute ischemic stroke treatment. Conflict of interest Jingjing Zhao, Wen Jiang, Yangdan Xie, and Zhongqing Sun. nothing to disclose Figure 1 - belongs to Background and aims Figure 2 - belongs to Methods Figure 3 - belongs to Results
Zhao et al. (2026) studied this question.