Post-cerebral ischemia energy crisis: the role of glucose metabolism in the energetic crisis

Cells universally employ an efficiency-driven metabolic switch mechanism during nutritional changes, growth, and differentiation, transitioning from oxidative phosphorylation (OXPHOS) to glycolysis to ensure survival under hypoxic conditions or high energy demands. In cerebral ischemia, inadequate blood supply causes oxygen and energy deprivation, prompting brain cells to initiate glycolytic reprogramming to meet urgent energy needs. While this adaptation is a temporary solution, it may lead to lactic acidosis, aggravated inflammation, and increased free radical production. Prolonged reperfusion with sustained glycolysis can exacerbate brain cell damage, potentially causing irreversible harm. This review systematically examines the dynamic changes in glucose metabolic transport mechanisms and the roles of immediate, early, intermediate, and late responder cells, along with their regulatory factors, in glycolytic reprogramming. Using a temporal analysis framework based on the body's natural response sequence to pathological events, we elucidate how cells at different stages collaborate to address glucose metabolism reprogramming under pathological conditions. Reversing glucose metabolism reprogramming and inhibiting glycolysis may improve the pathological processes of ischemic stroke, offering potential therapeutic benefits.