NDLI: Astrocytes Regulate Angiogenesis Through the Jagged1-Mediated Notch1 Pathway After Status Epilepticus

Content Provider	Springer Nature Link
Author	Zhai, Xuan Liang, Ping Li, Yingliang Li, Lusheng Zhou, Yudong Wu, Xuanxuan Deng, Jinmu Jiang, Li
Copyright Year	2015
Abstract	Vascular disruptions including blood–brain barrier breakdown and pathologic angiogenesis contribute to the development of epilepsy in normal brains. The Notch signaling pathway is activated in response to seizure activity, and its activation promotes seizures, although its exact role in angiogenesis is poorly understood. Here, we have examined the role of Notch signaling in angiogenesis in a kainic acid-induced mouse model of epilepsy. We show that following seizures, expression of the Notch ligand Jagged1 in the hippocampus is upregulated in astrocytes and levels of activated Notch1 are increased in endothelial cells. Using an in vitro model of angiogenesis, we provide evidence that brain endothelial tube formation is promoted in the presence of astrocytes. Isolated primary brain endothelial cells develop significantly longer vascular sprouts when cultured in the presence of astrocytes. Notch1 signaling is activated in brain endothelial cells cocultured with astrocytes, and astrocytic Jagged1 expression is required for angiogenic enhancement, as shown by the inhibitory effect of Jagged1 small interfering RNA (siRNA) expression in astrocytes on endothelial cell vascular sprouting in vitro. Therapies targeting the Jagged1/Notch1 signaling pathway may therefore be effective in limiting aberrant angiogenesis following status epilepticus.
Starting Page	5893
Ending Page	5901
Page Count	9
File Format	PDF
ISSN	08937648
Journal	Molecular Neurobiology
Volume Number	53
Issue Number	9
e-ISSN	15591182
Language	English
Publisher	Springer US
Publisher Date	2015-10-27
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Epilepsy Notch signaling Angiogenesis Astrocytes Endothelial cells Neurosciences Neurobiology Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Neurology Cellular and Molecular Neuroscience

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