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Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice

PURPOSE: Intracerebral hemorrhage (ICH) is a fatal disease without effective treatment. The damage of the blood–brain barrier (BBB) is a key cause of brain edema and herniation after ICH. Omarigliptin (also known as MK3102) is a potent antidiabetic that inhibits dipeptidyl peptidase (DPP4); the latt...

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Autores principales: Zhang, Yan, Liu, Yang, Zhang, Xiangyu, Yong, V Wee, Xue, Mengzhou
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Dove 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278948/
https://www.ncbi.nlm.nih.gov/pubmed/37342770
http://dx.doi.org/10.2147/JIR.S411017
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author Zhang, Yan
Liu, Yang
Zhang, Xiangyu
Yong, V Wee
Xue, Mengzhou
author_facet Zhang, Yan
Liu, Yang
Zhang, Xiangyu
Yong, V Wee
Xue, Mengzhou
author_sort Zhang, Yan
collection PubMed
description PURPOSE: Intracerebral hemorrhage (ICH) is a fatal disease without effective treatment. The damage of the blood–brain barrier (BBB) is a key cause of brain edema and herniation after ICH. Omarigliptin (also known as MK3102) is a potent antidiabetic that inhibits dipeptidyl peptidase (DPP4); the latter has the ability to bind and degrade matrix metalloproteinases (MMPs). The present study aims to investigate the protective effects of omarigliptin against the destruction of BBB following ICH in mice. METHODS AND MATERIALS: Collagenase VII was used to induce ICH in C57BL/6 mice. MK3102 (7 mg/kg/day) was administered after ICH. The modified neurological severity scores (mNSS) were carried out to assess neurological functions. Nissl staining was applied to evaluate neuronal loss. Brain water content, Evans blue extravasation, Western blots, immunohistochemistry and immunofluorescence were used to study the protective effects of BBB with MK3102 at 3 days after ICH. RESULTS: MK3102 reduced DPP4 expression and decreased hematoma formation and neurobehavioral deficits of ICH mice. This was correspondent with lowered activation of microglia/macrophages and infiltration of neutrophils after ICH. Importantly, MK3102 protected the integrity of the BBB after ICH, associated with decreased expression of MMP-9, and preservation of the tight junction proteins ZO-1 and Occludin on endothelial cells through putative degradation of MMP-9, and inhibition of the expression of CX43 on astrocytes. CONCLUSION: Omarigliptin protects the integrity of the BBB in mice after ICH injury.
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spelling pubmed-102789482023-06-20 Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice Zhang, Yan Liu, Yang Zhang, Xiangyu Yong, V Wee Xue, Mengzhou J Inflamm Res Original Research PURPOSE: Intracerebral hemorrhage (ICH) is a fatal disease without effective treatment. The damage of the blood–brain barrier (BBB) is a key cause of brain edema and herniation after ICH. Omarigliptin (also known as MK3102) is a potent antidiabetic that inhibits dipeptidyl peptidase (DPP4); the latter has the ability to bind and degrade matrix metalloproteinases (MMPs). The present study aims to investigate the protective effects of omarigliptin against the destruction of BBB following ICH in mice. METHODS AND MATERIALS: Collagenase VII was used to induce ICH in C57BL/6 mice. MK3102 (7 mg/kg/day) was administered after ICH. The modified neurological severity scores (mNSS) were carried out to assess neurological functions. Nissl staining was applied to evaluate neuronal loss. Brain water content, Evans blue extravasation, Western blots, immunohistochemistry and immunofluorescence were used to study the protective effects of BBB with MK3102 at 3 days after ICH. RESULTS: MK3102 reduced DPP4 expression and decreased hematoma formation and neurobehavioral deficits of ICH mice. This was correspondent with lowered activation of microglia/macrophages and infiltration of neutrophils after ICH. Importantly, MK3102 protected the integrity of the BBB after ICH, associated with decreased expression of MMP-9, and preservation of the tight junction proteins ZO-1 and Occludin on endothelial cells through putative degradation of MMP-9, and inhibition of the expression of CX43 on astrocytes. CONCLUSION: Omarigliptin protects the integrity of the BBB in mice after ICH injury. Dove 2023-06-15 /pmc/articles/PMC10278948/ /pubmed/37342770 http://dx.doi.org/10.2147/JIR.S411017 Text en © 2023 Zhang et al. https://creativecommons.org/licenses/by-nc/3.0/This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/ (https://creativecommons.org/licenses/by-nc/3.0/) ). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms (https://www.dovepress.com/terms.php).
spellingShingle Original Research
Zhang, Yan
Liu, Yang
Zhang, Xiangyu
Yong, V Wee
Xue, Mengzhou
Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice
title Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice
title_full Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice
title_fullStr Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice
title_full_unstemmed Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice
title_short Omarigliptin Protects the Integrity of the Blood–Brain Barrier After Intracerebral Hemorrhage in Mice
title_sort omarigliptin protects the integrity of the blood–brain barrier after intracerebral hemorrhage in mice
topic Original Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10278948/
https://www.ncbi.nlm.nih.gov/pubmed/37342770
http://dx.doi.org/10.2147/JIR.S411017
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