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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 |
Sumario: | 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. |
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