DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and nuclear factor κB in rats.

Gamma-secretase inhibitor, N-[N-(3,5-difluorophenacetyl)-1-alanyl]-S-phenylglycine t-butyl ester (DAPT) suppresses the activation of Notch 1 signaling, which is recognized as the cell fate signaling and may participate in inflammatory processes together with NF-κB pathway that contributes to the brain damage after stroke. DAPT has important pharmacological roles in many diseases. However, little is known about the effect of DAPT on NF-κB during cerebral ischemia. This study investigated the time course expression of Notch 1 and the effects of DAPT on Notch 1 and NF-jB after MCAO. The results showed that Notch 1 signaling was up-regulated at the early stage after MCAO, DAPT down-regulated the expression of Notch 1 and NF-κB and protected brain from damage caused by MCAO. These results may indicate that the downregulation of Notch 1–NF-κB pathway after ischemia by administration of DAPT is a potential mechanism for its protection.