Abstract
Ischemic stroke (IS) is a cerebrovascular disease with a high rate of disability and mortality. It is classified as the second leading cause of death that arises from the sudden occlusion of small vessels in the brain with consequent lack of oxygen and nutrients in the brain tissue. Following an acute ischemic event, the cascade of events promotes the activation of multiple signaling pathways responsible for irreversible neuronal damage. The mitogen-activated protein kinase (MAPK) signaling pathway transmits signals from the cell membrane to the nucleus in response to different stimuli, regulating proliferation, differentiation, inflammation, and apoptosis. Several lines of evidence showed that MAPK is an important regulator of ischemic and hemorrhagic cerebral vascular disease; indeed, it can impair blood–brain barrier (BBB) integrity and exacerbate neuroinflammation through the release of pro-inflammatory mediators implementing neurovascular damage after ischemic stroke. This review aims to illustrate the miRNAs involved in the regulation of MAPK in IS, in order to highlight possible targets for potential neuroprotective treatments. We also discuss some miRNAs (miR), including miR-145, miR-137, miR-493, and miR-126, that are important as they modulate processes such as apoptosis, neuroinflammation, neurogenesis, and angiogenesis through the regulation of the MAPK pathway in cerebral IS. To date, limited drug therapies are available for the treatment of IS; therefore, it is necessary to implement preclinical and clinical studies aimed at discovering novel therapeutic approaches to minimize post-stroke neurological damage.
Highlights
Stroke represents one of the main causes of mortality and morbidity in global health [1].Two pathological subtypes of stroke can be identified, which are ischemic stroke (IS) and hemorrhagic stroke [2]
This review provided an overview of the studies that demonstrated the involvement of miRNAs in the modulation of the mitogen-activated protein kinase (MAPK) pathway in IS
The evidence indicated that some miRNA are dysregulated in IS, influencing its pathogenesis through an altered regulation of the MAPK pathway
Summary
Stroke represents one of the main causes of mortality and morbidity in global health [1]. IS is induced by occlusion of small vessels in the brain and atherosclerosis affecting the cerebral circulation These events result in the interruption of blood flow and the death of the cerebral tissues. The reperfusion event following the cerebral ischemic attack promotes the activation of biochemical processes inducing overproduction of reactive oxygen species (ROS) and reactive nitrogen species (RNS) which are decisive in inducing pathological brain damage [1]. Several mechanisms are involved in IS pathogenesis, different evidence demonstrates that increased expression of mitogen-activated protein kinase (MAPK) in cerebral ischemia plays a key role in the activation of inflammatory processes [26,27]. Medicina 2021, 57, 1053 and to evaluate whether miRNAs in blood samples are useful as predictive and timely biomarkers of IS
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