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Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke
Optogenetics has been used to regulate astrocyte activity and modulate neuronal function after brain injury. Activated astrocytes regulate blood-brain barrier functions and are thereby involved in brain repair. However, the effect and molecular mechanism of optogenetic-activated astrocytes on the ch...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
JKL International LLC
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529757/ https://www.ncbi.nlm.nih.gov/pubmed/37196130 http://dx.doi.org/10.14336/AD.2023.0226 |
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author | Suo, Qian Deng, Lidong Chen, Tingting Wu, Shengju Qi, Lin Liu, Ze He, Tingting Tian, Heng-Li Li, Wanlu Tang, Yaohui Yang, Guo-Yuan Zhang, Zhijun |
author_facet | Suo, Qian Deng, Lidong Chen, Tingting Wu, Shengju Qi, Lin Liu, Ze He, Tingting Tian, Heng-Li Li, Wanlu Tang, Yaohui Yang, Guo-Yuan Zhang, Zhijun |
author_sort | Suo, Qian |
collection | PubMed |
description | Optogenetics has been used to regulate astrocyte activity and modulate neuronal function after brain injury. Activated astrocytes regulate blood-brain barrier functions and are thereby involved in brain repair. However, the effect and molecular mechanism of optogenetic-activated astrocytes on the change in barrier function in ischemic stroke remain obscure. In this study, adult male GFAP-ChR2-EYFP transgenic Sprague-Dawley rats were stimulated by optogenetics at 24, 36, 48, and 60 h after photothrombotic stroke to activate ipsilateral cortical astrocytes. The effects of activated astrocytes on barrier integrity and the underlying mechanisms were explored using immunostaining, western blotting, RT-qPCR, and shRNA interference. Neurobehavioral tests were performed to evaluate therapeutic efficacy. The results demonstrated that IgG leakage, gap formation of tight junction proteins, and matrix metallopeptidase 2 expression were reduced after optogenetic activation of astrocytes (p<0.05). Moreover, photo-stimulation of astrocytes protected neurons against apoptosis and improved neurobehavioral outcomes in stroke rats compared to controls (p<0.05). Notably, interleukin-10 expression in optogenetic-activated astrocytes significantly increased after ischemic stroke in rats. Inhibition of interleukin-10 in astrocytes compromised the protective effects of optogenetic-activated astrocytes (p<0.05). We found for the first time that interleukin-10 derived from optogenetic-activated astrocytes protected blood-brain barrier integrity by decreasing the activity of matrix metallopeptidase 2 and attenuated neuronal apoptosis, which provided a novel therapeutic approach and target in the acute stage of ischemic stroke. |
format | Online Article Text |
id | pubmed-10529757 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | JKL International LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-105297572023-10-01 Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke Suo, Qian Deng, Lidong Chen, Tingting Wu, Shengju Qi, Lin Liu, Ze He, Tingting Tian, Heng-Li Li, Wanlu Tang, Yaohui Yang, Guo-Yuan Zhang, Zhijun Aging Dis Original Article Optogenetics has been used to regulate astrocyte activity and modulate neuronal function after brain injury. Activated astrocytes regulate blood-brain barrier functions and are thereby involved in brain repair. However, the effect and molecular mechanism of optogenetic-activated astrocytes on the change in barrier function in ischemic stroke remain obscure. In this study, adult male GFAP-ChR2-EYFP transgenic Sprague-Dawley rats were stimulated by optogenetics at 24, 36, 48, and 60 h after photothrombotic stroke to activate ipsilateral cortical astrocytes. The effects of activated astrocytes on barrier integrity and the underlying mechanisms were explored using immunostaining, western blotting, RT-qPCR, and shRNA interference. Neurobehavioral tests were performed to evaluate therapeutic efficacy. The results demonstrated that IgG leakage, gap formation of tight junction proteins, and matrix metallopeptidase 2 expression were reduced after optogenetic activation of astrocytes (p<0.05). Moreover, photo-stimulation of astrocytes protected neurons against apoptosis and improved neurobehavioral outcomes in stroke rats compared to controls (p<0.05). Notably, interleukin-10 expression in optogenetic-activated astrocytes significantly increased after ischemic stroke in rats. Inhibition of interleukin-10 in astrocytes compromised the protective effects of optogenetic-activated astrocytes (p<0.05). We found for the first time that interleukin-10 derived from optogenetic-activated astrocytes protected blood-brain barrier integrity by decreasing the activity of matrix metallopeptidase 2 and attenuated neuronal apoptosis, which provided a novel therapeutic approach and target in the acute stage of ischemic stroke. JKL International LLC 2023-10-01 /pmc/articles/PMC10529757/ /pubmed/37196130 http://dx.doi.org/10.14336/AD.2023.0226 Text en copyright: © 2023 Suo et al. https://creativecommons.org/licenses/by/2.0/this is an open access article distributed under the terms of the creative commons attribution license, which permits unrestricted use, distribution and reproduction in any medium provided that the original work is properly attributed. |
spellingShingle | Original Article Suo, Qian Deng, Lidong Chen, Tingting Wu, Shengju Qi, Lin Liu, Ze He, Tingting Tian, Heng-Li Li, Wanlu Tang, Yaohui Yang, Guo-Yuan Zhang, Zhijun Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke |
title | Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke |
title_full | Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke |
title_fullStr | Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke |
title_full_unstemmed | Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke |
title_short | Optogenetic Activation of Astrocytes Reduces Blood-Brain Barrier Disruption via IL-10 In Stroke |
title_sort | optogenetic activation of astrocytes reduces blood-brain barrier disruption via il-10 in stroke |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10529757/ https://www.ncbi.nlm.nih.gov/pubmed/37196130 http://dx.doi.org/10.14336/AD.2023.0226 |
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