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Adropin preserves the blood‐brain barrier through a Notch1/Hes1 pathway after intracerebral hemorrhage in mice
Authors:Lingyan Yu  Zhengyang Lu  Sherrefa Burchell  Derek Nowrangi  Anatol Manaenko  Xue Li  Yang Xu  Ningbo Xu  Jiping Tang  Haibin Dai  John H Zhang
Institution:1. Department of Pharmacy, Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China;2. Departments of Anesthesiology and Basic Sciences, School of Medicine, Loma Linda University, Loma Linda, California, USA;3. Departments of Neurosurgery & Brain and Nerve Research Laboratory, The First Affiliated Hospital, Soochow University, Suzhou, China
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.
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Keywords:adropin  blood‐brain barrier  intracerebral hemorrhage  N‐cadherin  Notch1
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