SMAD4 and brain ischemia: In our study, Tp53 and miR-34a were upregulated, hence could inhibit Notch, Wnt and TGF-β signaling by targeting Dll1, Jag1, Wnt1, Wnt3 and Smad4. Tp53 was also reported to inhibit Hedgehog signalling [58], implicating that p53 and miR-34a may function as negative regulators of NPC proliferation by inhibiting Notch, Wnt, Hedgehog and TGF-β signaling pathway following cerebral ischemia.