Cerebral ischemia induces angiogenesis in the peri-infarct regions via Notch1 signaling activation

Changhong Ren, Yu Yao, Rongrong Han, Qingjian Huang, Haiyan Li, Brian Wang, Sijie Li, Ming Li, Ying Mao, Xiaoou Mao, Lin Xie, Liangfu Zhou, Jiangnan Hu, Xunming Ji, Kunlin Jin

Research output: Contribution to journalArticle

20 Scopus citations

Abstract

The Notch1 signaling pathway is considered as one of important regulators of angiogenesis during development, but its role in cerebral ischemia-induced angiogenesis is less well understood. Here, we used human and rodent brains to explore whether Notch1 signaling was involved in the angiogenesis after focal cerebral ischemia. Using immunohistochemistry on surgically resected ischemic stroke brain tissue, we found that the area, volume, and length of the blood vessels in the peri-infarct regions were significantly increased after ischemic stroke in humans, compared with non-ischemic stroke specimens. In addition, the expression of the activated form of Notch1 (Notch intracellular domain; NICD) was increased in endothelial cells of the peri-infarct region. The Notch1 ligand, Jagged1, also increased in abundance in the peri-infarct regions in human. We further confirmed that Notch1 signaling was activated in the peri-infarct regions in a mouse distal middle cerebral artery occlusion (dMCAO) model. Lentivirus-mediated Notch1 knockdown reduced ischemia-induced angiogenesis in the peri-infarct regions of the brain. Our findings suggest that ischemic stroke in human can also induce angiogenesis in the peri-infarct regions as does in animal models of focal ischemia and that Notch1 signaling plays a critical role in mediating this process, which may provide fundamental knowledge regarding the potential mechanisms underlying angiogenesis after ischemic stroke.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalExperimental Neurology
Volume304
DOIs
StatePublished - Jun 2018

Keywords

  • Angiogenesis
  • Infarction
  • Ischemic stroke
  • Notch1 signaling

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