1. Hypertonic saline mediates the NLRP3/IL-1β signaling axis in microglia to alleviate ischemic blood-brain barrier permeability by downregulating astrocyte-derived VEGF in rats.
- Author
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Wang QS, Ding HG, Chen SL, Liu XQ, Deng YY, Jiang WQ, Li Y, Huang LQ, Han YL, Wen MY, Wang MQ, and Zeng HK
- Subjects
- Animals, Capillary Permeability drug effects, Cells, Cultured, Disease Models, Animal, Down-Regulation, Male, Rats, Rats, Sprague-Dawley, Astrocytes drug effects, Astrocytes metabolism, Blood-Brain Barrier drug effects, Cerebral Infarction drug therapy, Inflammasomes drug effects, Interleukin-1beta drug effects, Microglia drug effects, Microglia metabolism, NLR Family, Pyrin Domain-Containing 3 Protein drug effects, Saline Solution, Hypertonic pharmacology, Vascular Endothelial Growth Factor A metabolism
- Abstract
Introduction: The aim of this study was to explore whether the antibrain edema of hypertonic saline (HS) is associated with alleviating ischemic blood-brain barrier (BBB) permeability by downregulating astrocyte-derived vascular endothelial growth factor (VEGF), which is mediated by microglia-derived NOD-like receptor protein 3 (NLRP3) inflammasome., Methods: The infarct volume and BBB permeability were detected. The protein expression level of VEGF in astrocytes in a transient focal brain ischemia model of rats was evaluated after 10% HS treatment. Changes in the NLRP3 inflammasome, IL-1β protein expression, and the interleukin-1 receptor (IL1R1)/pNF-кBp65/VEGF signaling pathway were determined in astrocytes., Results: HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulates IL-1β expression by inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulates VEGF expression by inhibiting the phosphorylation of NF-кBp65 mediated by IL-1β in astrocytes., Conclusions: HS alleviated the BBB permeability, reduced the infarct volume, and downregulated the expression of VEGF in astrocytes. HS downregulated IL-1β expression via inhibiting the activation of the NLRP3 inflammasome in microglia and then downregulated VEGF expression through inhibiting the phosphorylation of NF-кBp65 mediated by IL-1β in astrocytes., (© 2020 The Authors. CNS Neuroscience & Therapeutics Published by John Wiley & Sons Ltd.)
- Published
- 2020
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