Modulation of microglial phenotypes by dexmedetomidine through TREM2 reduces neuroinflammation in heatstroke
Abstract No FDA approved pharmacological therapy is available to reduce neuroinflammation following heatstroke. Previous studies have indicated that dexmedetomidine (DEX) could protect against inflammation and brain injury in various inflammation-associated diseases. However, no one has tested wheth...
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| Autores principales: | , , , , , , , , , , |
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| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Nature Portfolio
2021
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| Materias: | |
| Acceso en línea: | https://doaj.org/article/ffffee16cf03490599b2fb08328301bf |
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| Sumario: | Abstract No FDA approved pharmacological therapy is available to reduce neuroinflammation following heatstroke. Previous studies have indicated that dexmedetomidine (DEX) could protect against inflammation and brain injury in various inflammation-associated diseases. However, no one has tested whether DEX has neuro-protective effects in heatstroke. In this study, we focused on microglial phenotypic modulation to investigate the mechanisms underlying the anti-inflammatory effects of DEX in vivo and in vitro. We found that DEX treatment reduced the expression of CD68, iNOS, TNF-α, and IL-1β, and increased the expression of CD206, Arg1, IL-10 and TGF-β in microglia, ameliorating heatstroke induced neuroinflammation and brain injury in mice. TREM2, whose neuro-protective function has been validated by genetic studies in Alzheimer’s disease and Nasu-Hakola disease, was significantly promoted by DEX in the microglia. TREM2 esiRNA reversed the DEX-induced activation of PI3K/Akt signalling. Overall these findings indicated that DEX may serve, as a potential therapeutic approach to ameliorate heatstroke induced neuroinflammation and brain injury via TREM2 by activating PI3K/Akt signalling. |
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