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Ischemic stroke (IS) is a leading cause of death and disability worldwide. Currently, the main therapeutic strategy involves the use of intravenous thrombolysis to restore cerebral blood flow to prevent the transition of the penumbra to the infarct core. However, due to various limitations and complications, including the narrow time window in which this approach is effective, less than 10% of patients benefit from such therapy. Thus, there is an urgent need for alternative therapeutic strategies, with neuroprotection against the ischemic cascade response after IS being one of the most promising options. In the past few decades, polyphenolic compounds have shown great potential in animal models of IS because of their high biocompatibility and ability to target multiple ischemic cascade signaling pathways, although low bioavailability is an issue that limits the applications of several polyphenols. Here, we review the pathophysiological changes following cerebral ischemia and summarize the research progress regarding the applications of polyphenolic compounds in the treatment of IS over the past 5 years. Furthermore, we discuss several potential strategies for improving the bioavailability of polyphenolic compounds as well as some essential issues that remain to be addressed for the translation of the related therapies to the clinic.

Polyphenols for the Treatment of Ischemic Stroke: New Applications and Insights