NOTCH1 and ischemia: Notch1, Hes1 and Hes5, components of the Notch signaling pathway, were increased after ischemia, and further stimulated with folic acid supplementation.114 Experimental stroke via middle cerebral artery occlusion (MCAO) might lead to increased Notch signaling as a compensatory mechanism, and folic acid supplementation would thereby further stimulate Notch increasing this regenerative effect.