Intranuclear matrix metalloproteinases promote DNA damage and apoptosis induced by oxygen-glucose deprivation in neurons

► The role of MMPs in neuronal apoptosis was investigated in vivo and in vitro. ► In an animal model of stroke, a broad-spectrum MMP inhibitor was neuroprotective. ► In primary neurons, MMP-2 and -9 activities increased in the nucleus after OGD. ► Inhibition of MMP-2 and -9 prevented DNA damage and apoptosis in ischemic neurons. ► The results suggest a major role for intranuclear MMPs in neuronal apoptosis.