Neurological Sciences

, Volume 33, Issue 6, pp 1257–1264 | Cite as

DAPT protects brain against cerebral ischemia by down-regulating the expression of Notch 1 and Nuclear factor kappa B in rats

  • Shuya Li
  • Xiangjian Zhang
  • Yongjun Wang
  • Hui Ji
  • Yuanyuan Du
  • Haichao Liu
Original Article

Abstract

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-κB 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.

Keywords

Cerebral ischemia DAPT Notch 1 Nuclear factor kappa B Inflammation 

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Shuya Li
    • 1
  • Xiangjian Zhang
    • 2
  • Yongjun Wang
    • 1
  • Hui Ji
    • 2
  • Yuanyuan Du
    • 2
  • Haichao Liu
    • 2
  1. 1.Department of NeurologyBeijing Tiantan Hospital, Capital Medical UniversityBeijingChina
  2. 2.Department of NeurologySecond Hospital of Hebei Medical UniversityShijiazhuangChina

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