Adropin preserves the blood-brain barrier through a Notch1/Hes1 pathway after intracerebral hemorrhage in mice

Lingyan Yu, Zhengyang Lu, Sherrefa Burchell, Derek Nowrangi, Anatol Manaenko, Xue Li, Yang Xu, Ningbo Xu, Jiping Tang, Haibin Dai, John H. Zhang

Research output: Contribution to journalArticlepeer-review

Abstract

Adropin is expressed in the CNS and plays a crucial role in the development of stroke. However, little is currently known about the effects of adropin on the blood-brain barrier (BBB) function after intracerebral hemorrhage (ICH). In this study, the role of adropin in collagenase-induced ICH was investigated in mice. At 1-h post-ICH, mice were administered with recombinant human adropin by intranasal. Brain water +content, BBB permeability, and neurological function were measured at different time intervals. Proteins were quantified using western blot analysis, and the localizations of adropin and Notch1 were visualized via immunofluorescence staining. It is shown that adropin reduced brain water content and improved neurological functions. Adropin preserved the functionality of BBB by increasing N-cadherin expression and reducing extravasation of albumin. Moreover, in vivo knockdown of Notch1 and Hes1 both abolished the protective effects of adropin. Taken together, our data demonstrate that adropin constitutes a potential treatment value for ICH by preserving BBB and improving functional outcomes through the Notch1 signaling pathway.

Original languageEnglish
Pages (from-to)750-760
Number of pages11
JournalJournal of Neurochemistry
Volume143
Issue number6
DOIs
StatePublished - Dec 2017

ASJC Scopus Subject Areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Keywords

  • N-cadherin
  • Notch1
  • adropin
  • blood-brain barrier
  • intracerebral hemorrhage
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Male
  • Signal Transduction/physiology
  • Peptides/metabolism
  • Animals
  • Blood-Brain Barrier/drug effects
  • Cerebral Hemorrhage/metabolism
  • Mice
  • Receptor, Notch1/metabolism
  • Transcription Factor HES-1/metabolism
  • Blood Proteins/metabolism

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