The role of lactate and lactylation in ischemic stroke

Stroke is a leading cause of death and disability worldwide. Ischemic cell death resulting from inadequate blood oxygen and glucose supply is one of the main pathophysiological mechanisms of brain injury. Previous studies have highlighted the critical role of lactate in the physiological and pathological processes of brain tissue, and the changes in lactate levels are crucial in the occurrence and progression of stroke. Lactylation represent a newly discovered process of post-translational modification of proteins, which exerts key physiological and pathological roles in stroke by influencing the lactylation of both histones and non-histones. Here, we review the current research progress on lactate and lactylation in ischemic stroke (IS), discussing the bidirectional regulatory effects of energy metabolism and lactate on inflammatory responses, oxidative stress, neurotoxicity, and neuroplasticity, as well as the cerebrovascular system, along with the effects of lactylation modifications on glycolytic reprogramming and immune function. This new evidence provides broader insights into the epigenetic mechanisms in IS and aids in assessing the feasibility of targeting lactate /lactylation for the treatment of IS.