Ischemic brain edema: Emerging cellular mechanisms and therapeutic approaches

Brain edema is one of the most devastating consequences of ischemic stroke. Malignant cerebral edema is the main reason accounting for the high mortality rate of large hemispheric strokes. Despite decades of tremendous efforts to elucidate mechanisms underlying the formation of ischemic brain edema and search for therapeutic targets, current treatments for ischemic brain edema remain largely symptom-relieving rather than aiming to stop the formation and progression of edema. Recent preclinical research reveals novel cellular mechanisms underlying edema formation after brain ischemia and reperfusion. Advancement in neuroimaging techniques also offers opportunities for early diagnosis and prediction of malignant brain edema in stroke patients to rapidly adopt life-saving surgical interventions. As reperfusion therapies become increasingly used in clinical practice, understanding how therapeutic reperfusion influences the formation of cerebral edema after ischemic stroke is critical for decision-making and post-reperfusion management. In this review, we summarize these research advances in the past decade on the cellular mechanisms, and evaluation, prediction, and intervention of ischemic brain edema in clinical settings, aiming to provide insight into future preclinical and clinical research on the diagnosis and treatment of brain edema after stroke.