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...

Descripción completa

Detalles Bibliográficos
Autores principales: 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
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