Our previous study [10] demonstrated that cerebral ischemia/reperfusion injury caused by MCAO triggered the cleavage of caspase-3, and the level of the cleaved caspase-3 was suppressed by MANF treatment, which suggests that the neuroprotective effects of MANF in the ischemic cerebral cortex may be intermediated by inhibiting cell apoptosis. Here, CASP3 is linked to brain ischemia.