Besides, it has also been reported that ischemic stroke increases HIF-1α expression levels, which could directly bind with NICD and NF-κB.197,198 Inhibition of both γ-secretase/Notch and HIF-1α significantly reduced cell apoptosis, while enhanced expression of NICD and HIF-1α increased NF-kB levels. This evidence concerns the gene NOTCH1 and ischemic stroke.