RIPK1 and ischemia: We also demonstrated that ischemia-induced RIPK1-mediated RIPK3/MLKL necroptosis was specific because Nec-1 treatment could significantly inhibit ischemia-induced increase of RIPK3, MLKL and p-MLKL expressions as well as attenuate ischemic brain injury via inhibition of RIPK1 kinase activity (Fig. 4 and Fig. 5A, B-D).