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Published in: NeuroMolecular Medicine 1/2014

01-03-2014 | Original Paper

The Neuroprotective Effects of Isoflurane Preconditioning in a Murine Transient Global Cerebral Ischemia–Reperfusion Model: The Role of the Notch Signaling Pathway

Authors: Hao-peng Zhang, Yan-yan Sun, Xiao-mei Chen, Li-bang Yuan, Bin-xiao Su, Rui Ma, Rui-ni Zhao, Hai-long Dong, Lize Xiong

Published in: NeuroMolecular Medicine | Issue 1/2014

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Abstract

Inhalational anesthetic preconditioning can induce neuroprotective effects, and the notch signaling pathway plays an important role in neural progenitor cell differentiation and the inflammatory response after central nervous system injury. This study evaluated whether the neuroprotective effect of isoflurane preconditioning is mediated by the activation of the notch signaling pathway. Mice were divided into two groups consisting of those that did or did not receive preconditioning with isoflurane. The expression levels of notch-1, notch intracellular domain (NICD), and hairy and enhancer of split (HES-1) were measured in mice subjected to transient global cerebral ischemia–reperfusion injury. The notch signaling inhibitor DAPT and conditional notch-RBP-J knockout mice were used to investigate the mechanisms of isoflurane preconditioning-induced neuroprotection. Immunohistochemical staining, real-time polymerase chain reaction assays, and Western blotting were performed. Isoflurane preconditioning induced neuroprotection against global cerebral ischemia. Preconditioning up-regulated the expression of notch-1, HES-1, and NICD after ischemic–reperfusion. However, these molecules were down-regulated at 72 h after ischemic–reperfusion. The inhibition of notch signaling activity by DAPT significantly attenuated the isoflurane preconditioning-induced neuroprotection, and similar results were obtained using notch knockout mice. Our results demonstrate that the neuroprotective effects of isoflurane preconditioning are mediated by the pre-activation of the notch signaling pathway.
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Metadata
Title
The Neuroprotective Effects of Isoflurane Preconditioning in a Murine Transient Global Cerebral Ischemia–Reperfusion Model: The Role of the Notch Signaling Pathway
Authors
Hao-peng Zhang
Yan-yan Sun
Xiao-mei Chen
Li-bang Yuan
Bin-xiao Su
Rui Ma
Rui-ni Zhao
Hai-long Dong
Lize Xiong
Publication date
01-03-2014
Publisher
Springer US
Published in
NeuroMolecular Medicine / Issue 1/2014
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-013-8273-7

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