Mechanisms of Autophagy in Ineffective Reperfusion After Ischemic Stroke

ABSTRACT Despite significant advancements in achieving high recanalization rates (80%–90%) for large vessel occlusions through mechanical thrombectomy, the issue of “futile recanalization” remains a major clinical challenge. Futile recanalization occurs when over half of patients fail to experience expected symptom improvement after vessel recanalization, often resulting in severe functional impairment or death. Traditionally, this phenomenon has been attributed to inadequate blood flow and reperfusion injury. More recently, ongoing neuronal death after reperfusion, which leads to the progression of the ischemic penumbra into the core infarct, has been termed “futile reperfusion.” This review explores the complex role of autophagy mechanisms in futile reperfusion following ischemic stroke, with a focus on its relationship to neuronal survival. We also examine the regulation of autophagic activity by epigenetic mechanisms. By investigating autophagy's role in ischemic stroke, we aim to identify novel pathways for precision treatment.