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Thrombin promotes pericyte coverage by Tie2 activation in a rat model of intracerebral hemorrhage.

Authors
  • Hu, En1
  • Hu, Wang1
  • Yang, Ali2
  • Zhou, Huajun3
  • Zhou, Jun4
  • Luo, Jiekun1
  • Wang, Yang1
  • Tang, Tao1
  • Cui, Hanjin5
  • 1 Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. , (China)
  • 2 Institute of Neurology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China; Department of Neurology, Henan Provincial People's Hospital, Zhengzhou, Henan 450003, China. , (China)
  • 3 Institute of Neurology, The First College of Clinical Medical Sciences, China Three Gorges University, Yichang, Hubei 443002, China. , (China)
  • 4 Institute of Medical Science, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. , (China)
  • 5 Institute of Integrative Medicine, Xiangya Hospital, Central South University, Changsha, Hunan 410008, China. Electronic address: [email protected] , (China)
Type
Published Article
Journal
Brain research
Publication Date
Apr 01, 2019
Volume
1708
Pages
58–68
Identifiers
DOI: 10.1016/j.brainres.2018.12.003
PMID: 30527680
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Pericyte coverage on the endothelial tubes leads to the formation of a mature and stable microvessel system, which is critical for brain repair after intracerebral hemorrhage (ICH). We report herein that thrombin promotes pericyte coverage by activating Tie2 and the downstream signaling pathway PI3K/Akt in a rat model of ICH. ICH was induced by injection of autologous blood with or without thrombin inhibitor hirudin. Rats were treated with thrombin alone or in combination with a Tie2 inhibitor. The expression of total- and phospho-Tie2, PI3K and phospho-Akt, blood perfusion, pericyte coverage, IgG extravasation, neuron survival and neurological deficits were evaluated by western blot, fluorescein-5-isothiocyanate-dextran staining, immunohistochemistry, Nissl staining and modified neurological severity scores respectively. Induction of ICH resulted in increased phosphorylation of Tie2 on endothelial cells and pericyte coverage, better formation of integral and functional microvessels, more surviving neurons and accelerated motor function recovery, all of which were significantly attenuated by hirudin at 7 and 14 days after ICH induction. Furthermore, thrombin increased phosphorylation of Tie2 and Akt, expression of PI3K, and pericyte coverage, which were however reversed by pharmacological inhibition of Tie2. Our results demonstrated that thrombin promotes pericyte coverage on microvessels following ICH by enhancing activation of Tie2, in which the downstream PI3K/Akt signaling pathway might be involved. Copyright © 2018 Elsevier B.V. All rights reserved.

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