Cargando…
Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke
Intracerebral hemorrhage (ICH) is a major cause of stroke, with high mortality and morbidity. There is no effective pharmacological therapy for ICH. Previous studies have indicated that CXCR4 antagonists reduced microglia activation, attenuated infiltration of T cells, and improved functional recove...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582767/ https://www.ncbi.nlm.nih.gov/pubmed/32992950 http://dx.doi.org/10.3390/ijms21197085 |
_version_ | 1783599267495018496 |
---|---|
author | Yu, Seong-Jin Wu, Kuo-Jen Wang, Yu-Syuan Song, Jen-Shin Wu, Chien-Huang Jan, Jiing-Jyh Bae, Eunkyung Chen, Hsi Shia, Kak-Shan Wang, Yun |
author_facet | Yu, Seong-Jin Wu, Kuo-Jen Wang, Yu-Syuan Song, Jen-Shin Wu, Chien-Huang Jan, Jiing-Jyh Bae, Eunkyung Chen, Hsi Shia, Kak-Shan Wang, Yun |
author_sort | Yu, Seong-Jin |
collection | PubMed |
description | Intracerebral hemorrhage (ICH) is a major cause of stroke, with high mortality and morbidity. There is no effective pharmacological therapy for ICH. Previous studies have indicated that CXCR4 antagonists reduced microglia activation, attenuated infiltration of T cells, and improved functional recovery in ischemic stroke animals. The interaction of CXCR4 antagonists and ICH has not been characterized. The purpose of this study is to examine the neuroprotective action of a novel CXCR4 antagonist CX807 against ICH. In primary cortical neuronal and BV2 microglia co-culture, CX807 reduced glutamate-mediated neuronal loss and microglia activation. Adult rats were locally administered with collagenase VII to induce ICH. CX807 was given systemically after the ICH. Early post-treatment with CX807 improved locomotor activity in ICH rats. Brain tissues were collected for qRTPCR and histological staining. ICH upregulated the expression of CXCR4, CD8, TNFα, IL6, and TLR4. The immunoreactivity of IBA1 and CD8, as well as TUNEL labeling, were enhanced in the perilesioned area. CX807 significantly mitigated these responses. In conclusion, our data suggest that CX807 is neuroprotective and anti-inflammatory against ICH. CX807 may have clinical implications for the treatment of hemorrhagic stroke. |
format | Online Article Text |
id | pubmed-7582767 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-75827672020-10-28 Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke Yu, Seong-Jin Wu, Kuo-Jen Wang, Yu-Syuan Song, Jen-Shin Wu, Chien-Huang Jan, Jiing-Jyh Bae, Eunkyung Chen, Hsi Shia, Kak-Shan Wang, Yun Int J Mol Sci Article Intracerebral hemorrhage (ICH) is a major cause of stroke, with high mortality and morbidity. There is no effective pharmacological therapy for ICH. Previous studies have indicated that CXCR4 antagonists reduced microglia activation, attenuated infiltration of T cells, and improved functional recovery in ischemic stroke animals. The interaction of CXCR4 antagonists and ICH has not been characterized. The purpose of this study is to examine the neuroprotective action of a novel CXCR4 antagonist CX807 against ICH. In primary cortical neuronal and BV2 microglia co-culture, CX807 reduced glutamate-mediated neuronal loss and microglia activation. Adult rats were locally administered with collagenase VII to induce ICH. CX807 was given systemically after the ICH. Early post-treatment with CX807 improved locomotor activity in ICH rats. Brain tissues were collected for qRTPCR and histological staining. ICH upregulated the expression of CXCR4, CD8, TNFα, IL6, and TLR4. The immunoreactivity of IBA1 and CD8, as well as TUNEL labeling, were enhanced in the perilesioned area. CX807 significantly mitigated these responses. In conclusion, our data suggest that CX807 is neuroprotective and anti-inflammatory against ICH. CX807 may have clinical implications for the treatment of hemorrhagic stroke. MDPI 2020-09-25 /pmc/articles/PMC7582767/ /pubmed/32992950 http://dx.doi.org/10.3390/ijms21197085 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Yu, Seong-Jin Wu, Kuo-Jen Wang, Yu-Syuan Song, Jen-Shin Wu, Chien-Huang Jan, Jiing-Jyh Bae, Eunkyung Chen, Hsi Shia, Kak-Shan Wang, Yun Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke |
title | Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke |
title_full | Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke |
title_fullStr | Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke |
title_full_unstemmed | Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke |
title_short | Protective Effect of CXCR4 Antagonist CX807 in a Rat Model of Hemorrhagic Stroke |
title_sort | protective effect of cxcr4 antagonist cx807 in a rat model of hemorrhagic stroke |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7582767/ https://www.ncbi.nlm.nih.gov/pubmed/32992950 http://dx.doi.org/10.3390/ijms21197085 |
work_keys_str_mv | AT yuseongjin protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT wukuojen protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT wangyusyuan protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT songjenshin protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT wuchienhuang protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT janjiingjyh protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT baeeunkyung protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT chenhsi protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT shiakakshan protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke AT wangyun protectiveeffectofcxcr4antagonistcx807inaratmodelofhemorrhagicstroke |