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Front. Pharmacol. | doi: 10.3389/fphar.2019.00153

Critical Role of Nrf2 in Experimental Ischemic Stroke

  • 1Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease and McKnight Brain Institute, University of Florida, United States

Ischemic stroke is one of the leading causes of death and long-term disability worldwide; however, effective clinical approaches are still limited. The transcriptional factor Nrf2 is a master regulator in cellular and organismal defense against endogenous and exogenous stressors by coordinating basal and stress-inducible activation of multiple cytoprotective genes. The Nrf2 network not only tightly controls redox homeostasis but also regulates multiple intermediary metabolic processes. Therefore, targeting Nrf2 has emerged as an attractive therapeutic strategy for the prevention and treatment of CNS diseases including stroke. Here, the current understanding of the Nrf2 regulatory network is critically examined to present evidence for the contribution of Nrf2 pathway in rodent ischemic stroke models. This review outlines the literature for Nrf2 studies in preclinical stroke and focuses on the in vivo evidence for the role of Nrf2 in primary and secondary brain injuries. The dynamic regulation of Nrf2 signaling, functional importance and its targeted intervention is revealed in permanent, transient, and global cerebral ischemia models. In addition, key considerations, pitfalls, and future potentials for Nrf2 studies in preclinical stroke investigation are discussed.

Keywords: Nrf2, Stroke, Antioxidant response element, middle cerebral artery occlusion, permanent MCAO, Transient MCAO, Global cerebral ischemia, preclinical models

Received: 26 Oct 2018; Accepted: 08 Feb 2019.

Edited by:

Javier Egea, Institute of Health Research of the University Hospital of La Princesa, Spain

Reviewed by:

Alexander A. Mongin, Albany Medical College, United States
Siew H. Gan, Monash University Malaysia, Malaysia  

Copyright: © 2019 Liu, Locascio and Doré. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: Prof. Sylvain Doré, University of Florida, Department of Anesthesiology, Center for Translational Research in Neurodegenerative Disease and McKnight Brain Institute, Gainesville, 02111, Florida, United States, sdore@ufl.edu