The cell-specific roles of Nrf2 in acute and chronic phases of ischemic stroke

Abstract

Ischemic stroke refers to the sudden loss of blood flow in a specific area of the brain. It is the fifth leading cause of mortality and the leading cause of permanent disability. The transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) controls the production of several antioxidants and protective proteins and it has been investigated as a possible pharmaceutical target for reducing harmful oxidative events in brain ischemia. Each cell type exhibits different roles and behaviors in different phases post-stroke, which is comprehensive yet important to understand to optimize management strategies and goals for care for stroke patients. In this review, we comprehensively summarize the protective effects of Nrf2 in experimental ischemic stroke, emphasizing the role of Nrf2 in different cell types including neurons, astrocytes, oligodendrocytes, microglia, and endothelial cells during acute and chronic phases of stroke and providing insights on the neuroprotective role of Nrf2 on each cell type throughout the long term of stroke care. We also highlight the importance of targeting Nrf2 in clinical settings while considering a variety of important factors such as age, drug dosage, delivery route, and time of administration.

Keywords: MCAO; astrocytes; endothelial cells; ischemic preconditioning; microglia; neurons; neuroprotection; oligodendrocytes; oxidative stress.

FIGURE 1

Cell‐specific effects of Nrf2 on ischemic stroke pathologies. Schematic image showing potential Nrf2 targets in acute and chronic recovery phases of ischemic stroke. BBB, blood–brain barrier; EC, endothelial cell; OPC, oligodendrocyte precursor cell; ROS, reactive oxygen species.