Melatonin is a potent free radical scavenger with excellent blood-brain barrier (BBB) permeability [10–12], which protects against focal cerebral ischemia in the mouse [13–17] and rat [18–20] by increasing phosphorylated Akt, increasing anti-apoptotic Bcl-xL, decreasing pro-apoptotic Bax, decreasing neuronal NO synthase (nNOS), decreasing inducible NO synthase (iNOS), increasing endothelial NO synthase (eNOS) and decreasing activated caspase-3 proteins. This evidence concerns the gene NOS2 and brain ischemia.