After cerebral ischemia–reperfusion, the expression of activated caspase-3 in the brain increases, and at the same time, the level of phosphorylated CREB increases correspondingly to resist apoptosis; however, the level of CREB in the brain decreases significantly, which is not conducive in inhibiting apoptosis (Zhang et al., 2010; Yu et al., 2016). Here, CREB1 is linked to brain ischemia.