NDLI: Acute Blockage of Notch Signaling by DAPT Induces Neuroprotection and Neurogenesis in the Neonatal Rat Brain After Stroke

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Acute Blockage of Notch Signaling by DAPT Induces Neuroprotection and Neurogenesis in the Neonatal Rat Brain After Stroke

Content Provider	Springer Nature Link
Author	Li, Zhongxia Wang, Jiangping Zhao, Congying Ren, Keming Xia, Zhezhi Yu, Huimin Jiang, Kewen
Copyright Year	2015
Abstract	Notch signaling is critically involved in various biological events. Notch undergoes cleavage by the γ-secretase enzyme to release Notch intracellular domain that will translocate into nucleus to result in expression of target gene. γ-Secretase inhibitors have been developed as potential treatments for neurological degenerative diseases, but its effects against ischemic injury remain relatively uncertain. In the present study, we demonstrated that N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester (DAPT), a γ-secretase inhibitor not only rescued the cerebral hypoperfusion or ischemia neonatal rats from death, reduced apoptosis in penumbra, but also reduced brain infarct size. Furthermore, DAPT elicited some morphologic hallmarks such as neurogenesis and angiogenesis that related to the brain repair and functional recovery after stroke: increased accumulations of newborn cells in the peri-infarct region with a higher fraction of them adopting immature neuronal and glial markers instead of microglial markers on 5 days, enhanced vascular densities in penumbra at 14 days, and evident regulations of the gene profiles associated with neurogenesis in penumbral tissues. The current results suggest that DAPT is a potential neuroprotectants against ischemic injury in immature brain, and future treatment strategies such as clinical trials using γ-secretase inhibitors would be an attractive therapy for perinatal ischemia.
Starting Page	132
Ending Page	140
Page Count	9
File Format	PDF
ISSN	18684483
Journal	Translational Stroke Research
Volume Number	7
Issue Number	2
e-ISSN	1868601X
Language	English
Publisher	Springer US
Publisher Date	2015-12-22
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	N-[N-(3, 5-difluorophenacetyl)-l-alanyl]-S-phenylglycine t-butyl ester Notch signaling Ischemia Neuroprotection Neurogenesis Angiogenesis Neurosciences Neurology Cardiology Neurosurgery Vascular Surgery
Content Type	Text
Resource Type	Article
Subject	Cardiology and Cardiovascular Medicine Neuroscience Neurology (clinical)

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