AKT1 and brain ischemia: In addition, NMDAR can also directly activate Akt through a non-canonical mechanism that involves the activation of calcium-calmodulin-dependent protein kinase in a PI3K-dependent manner.[68,69] Meanwhile, many previous studies have shown that inhibited Akt activation can lead to cerebral ischemia-induced neuronal death, whereas activation of Akt expression increases neural recovery after cerebral IRI.[70–72]