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

Abstract

Adropin is expressed in the central nervous system (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.

Adropin Contributes to Anti-Atherosclerosis by Suppressing Monocyte-Endothelial Cell Adhesion and Smooth Muscle Cell Proliferation

“…The remaining 16 mice were divided into three groups of six, five, and five mice, and infused using osmotic minipumps (Alzet Model 1002; Durect, Cupertino, CA, USA) for 4 weeks with three doses of adropin (0, 5, 10 μg/kg/h), respectively. Doses of adropin were selected based on previous data [ 5 , 9 , 28 , 29 ]. Pumps were implanted subcutaneously into the dorsum, and replaced once every 2 weeks under medetomidine-midazolam-butorphanol anesthesia [ 45 ].…”

“…Adropin reduces the permeability in rat brain microvascular ECs under ischemic conditions (hypoxia/low glucose) [ 8 ]. Adropin also preserves the blood–brain barrier function for intracerebral hemorrhage via the Notch1 signaling pathway in mice [ 9 ]. Adropin ameliorates murine limb perfusion and increases capillary density following hindlimb ischemia in mice [ 6 ].…”

Adropin: An endocrine link between the biological clock and cholesterol homeostasis

“…For example, adropin 34−76 alters whole body glucose and lipid metabolism when administered to mice [1] , [2] , rats [3] , [4] , and also activates signaling pathways in mammalian cell lines [5] . Adropin 34−76 may also function to preserve the circulatory system, regulating endothelial function and activity of endothelial nitric oxide synthase [5] , [6] , [7] , [8] . The Enho transcript is however widely expressed, with high levels of expression in the nervous system relative to other tissues in B6 mice [1] , [5] , [9] .…”

MST4 Kinase Inhibitor Hesperadin Attenuates Autophagy and Behavioral Disorder via the MST4/AKT Pathway in Intracerebral Hemorrhage Mice

“…Despite much research on ICH pathology, effective neuroprotective therapy remains limited [21,22]. The pathological mechanism associated with ICH is complex and involves dif-ferent cell signaling pathways, resulting in neuronal death and cell stress injury.…”