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Cerebral ischemia represents the third cause of death and the first cause of disability in adults. This process results from decreasing cerebral blood flow levels as a result of the occlusion of a major cerebral artery. This restriction in blood supply generates low levels of oxygen and glucose, which leads to a decrease in the energy metabolism of the cell, producing inflammation, and finally, neurological deterioration. Currently, blood restoration of flow is the only effective approach as a therapy in terms of ischemic stroke. However, a significant number of patients still have a poor prognosis, probably owing to the increase in the generation of reactive oxygen species (ROS) during the reperfusion of damaged tissue. Oxidative stress and inflammation can be avoided by modulating mitochondrial function and have been identified as potential targets for the treatment of cerebral ischemia. In recent years, the beneficial actions of flavonoids and polyphenols against cerebrovascular diseases have been extensively investigated. The use of resveratrol (RSV) has been shown to markedly decrease brain damage caused by ischemia in numerous studies. According to in vitro and in vivo experiments, there is growing evidence that RSV is involved in several pathways, including cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation, gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition.
2. Neuroprotective Mechanism Associated with Treatments Involving Resveratrol
2.1. Regulation of cAMP/AMPK/SIRT1 Pathway
2.2. Modulating JAK/ERK/STAT Signaling Pathway
2.3. Regulation of TLR4 Signal Transduction
2.4. Mechanism Targeting Gut/Brain Axis
2.5. Inhibition of GLUT3 Up-Regulation
2.6. Activation of Neuronal Autophagy
2.7. Via De Novo SUR1 Expression Inhibition
2.8. Administration of Resveratrol-Loaded Nanoparticles (NPs)
Herein we collected various recent studies describing the evaluation of the RSV effectiveness in the treatment of ischemic brain injury in different rodent animal models. RSV itself shares common properties with other polyphenol derivatives such as neuroprotection, anti-apoptotic, anti-inflammatory, and antioxidant characteristics. This has allowed RSV to be considered a promising small molecule drug for the treatment of age-related disorders. In this regard, data experiments collected from recent studies have shown different mechanisms of action in which RSV plays important roles in the management of the disease, such as cAMP/AMPK/SIRT1 regulation, JAK/ERK/STAT signaling pathway modulation, TLR4 signal transduction regulation gut/brain axis modulation, GLUT3 up-regulation inhibition, neuronal autophagy activation, and de novo SUR1 expression inhibition. The in vivo experiments that have been selected for this review may open novel perspectives and challenges for ischemic brain injuries with the potential to be translated from bench to bedside. While RSV has exhibited remarkable activities when it has been systemically administered, its poor bioavailability makes this drug unsuitable for clinical use. Interestingly, novel encapsulation strategies and the use of nanotechnology have emerged to overcome these drawbacks and might facilitate the transport of RSV at a specific site of action. Despite the fact that there are still no effective drugs approved for the treatment of cerebral ischemia, additional and detailed preclinical experiments should be performed involving a range of animal models with the aim to afford the most efficient therapy strategies, including new encapsulation techniques and the use of RSV-load NPs.
The entry is from 10.3390/neurosci2030022
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