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We specifically highlight natural flavonoids such as Baicalin, Baicalein, Chrysin, Vitexin, Galangin, Quercetin, Isoquercetin, Eriodictyol, Proanthocyanidin, (−)-epigallocatechin-3-gallate, Dihydromyricetin, Soybean Isoflavones, Calycosin, Icariside II, and Safflower Yellow, which have shown promising results in animal models of acute CNS injuries, including ischemic stroke, cerebral ischemia-reperfusion injury, intracerebral hemorrhage, subarachnoid hemorrhage, traumatic brain injury, and spinal cord injury