Beyond recanalization: integrating neuroimaging, cytoprotection and endovascular strategies in acute ischemic stroke

Ischemic stroke remains a leading cause of mortality and long-term disability worldwide. Although endovascular therapy has revolutionized the treatment of large vessel occlusion, a substantial proportion of patients fail to achieve functional independence. Critical challenges include the narrow therapeutic time window, suboptimal patient selection, difficulties in first-pass effect, and futile reperfusion driven by no-reflow phenomenon, reocclusion, ischemia-reperfusion injury, hemorrhagic transformation, and malignant cerebral edema, underscoring the need for more effective integrated strategies to promote patient recovery. This review provides a comprehensive synthesis of the underlying mechanisms and emerging interventions to address these obstacles. We first discuss how the integration of advanced neuroimaging, predictive biomarkers and artificial intelligence may refine prognostic predictions and patient selection criteria. Emerging cerebral cytoprotective strategies have gained attention for their ability to stabilize brain energy metabolism, and their potential to extend the therapeutic window and mitigate reperfusion injury warrants further investigation. Current endovascular strategies are examined, including device innovations, optimized bridging thrombolysis strategies, and tailored adjuvant antithrombotic regimens. Furthermore, we highlight preclinical evidence supporting the therapeutic potential of targeting mitochondrial and microvascular function, and the glymphatic system, which may help reduce the risk of futile reperfusion. Despite these advances, clinical translation remains hindered by oversimplified preclinical models, and the absence of patient stratification for tailored cytoprotection, gaps that demand model optimization and precision biomarkers. Progress in neuroimaging, cytoprotection, and endovascular strategies is contributing to the evolution of peri‑EVT management toward more integrated interventions, which may help translate successful recanalization into potential functional gains. Narrow time windows, no-reflow and reperfusion injury remain major limitations of EVT. Multimodal neuroimaging, AI and biomarkers may transform EVT patient selection. Novel cerebral cytoprotection stabilizes energy metabolism and may extend EVT time windows. Preserving glycocalyx, pericytes, and mitochondria may reduce the risk of no-reflow and reperfusion injury. Comprehensive peri-EVT strategies may improve ischemic stroke outcomes.