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Aims The lack of effective treatments for ischemic stroke is concerning. Here, we aimed to examine the protective effects of sestrin2 in ischemic stroke and determine the mechanism by which sestrin2 attenuates cerebral injuries. Main methods Ischemic stroke was induced in Sprague-Dawley rats using a photothrombotic ischemia (PTI) model. After sestrin2 was overexpressed or silenced, neurological deficits and brain infarction were evaluated. Cerebral angiogenesis and the expression of related proteins were examined by Western blotting an