Abstract
Ischemic stroke, characterized by the sudden loss of blood flow in specific area(s) of the brain, is the leading cause of permanent disability and is among the leading causes of death worldwide. The only approved pharmacological treatment for acute ischemic stroke (intravenous thrombolysis with recombinant tissue plasminogen activator) has significant clinical limitations and does not consider the complex set of events taking place after the onset of ischemic stroke (ischemic cascade), which is characterized by significant pro-oxidative events. The transcription factor Nuclear factor erythroid 2-related factor 2 (Nrf2), which regulates the expression of a great number of antioxidant and/or defense proteins, has been pointed as a potential pharmacological target involved in the mitigation of deleterious oxidative events taking place at the ischemic cascade. This review summarizes studies concerning the protective role of Nrf2 in experimental models of ischemic stroke, emphasizing molecular events resulting from ischemic stroke that are, in parallel, modulated by Nrf2. Considering the acute nature of ischemic stroke, we discuss the challenges in using a putative pharmacological strategy (Nrf2 activator) that relies upon transcription, translation and metabolically active cells in treating ischemic stroke patients.
Highlights
Ischemic stroke, the most common one, accounts for approximately 87% of all stroke cases
Among the non-modifiable risk factors, the most important ones are (i) age, (ii) sex, (iii) ethnicity (Hispanic and black populations are at higher risk of stroke than white populations [5]) and (iv) genetics
Among the potential oxidative stress-related molecular targets, the transcription factor Nrf2 (Nuclear factor erythroid 2-related factor 2), which regulates the expression of a great number of antioxidant and/or defense proteins, has been pointed as a potential pharmacological target involved in the mitigation of deleterious oxidative events taking place at the ischemic cascade
Summary
The most common one, accounts for approximately 87% of all stroke cases. Intravenous thrombolysis with recombinant tissue plasminogen activator is the only approved pharmacological treatment for acute ischemic stroke It has significant beneficial effects in acute ischemic stroke when administered between 3 and 4.5 h after the onset of symptoms [15], an extension of this time interval is currently under debate [16]. This thrombolytic treatment aims at stimulating fibrinolysis to allow for clot removal, but does not consider the complex set of events taking place after the onset of ischemic stroke, called ischemic cascade (discussed below). We reviewed the available experimental literature concerning the effects of Nrf activators in ischemic stroke models, discussing the potential pharmacological use of Nrf activators in ischemic stroke patients
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