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The cystathionine β-synthase/hydrogen sulfide pathway contributes to microglia-mediated neuroinflammation following cerebral ischemia.
- Source :
-
Brain, Behavior & Immunity . Nov2017, Vol. 66, p332-346. 15p. - Publication Year :
- 2017
-
Abstract
- The mechanisms underlying neuroinflammation following cerebral ischemia remain unclear. Hydrogen sulfide (H 2 S), a newly identified gasotransmitter, has been reported to regulate inflammation. In the current study, we investigated whether the endogenous H 2 S production pathway contributed to microglia-mediated neuroinflammation following stroke. We used a mouse middle cerebral artery occlusion (MCAO) model and an in vitro cellular model to mimic ischemia-induced microglial neuroinflammation. Expression of the H 2 S synthase cystathionine β-synthase (CBS) and H 2 S synthetic activity were rapidly decreased in the ischemic brain tissue following MCAO. Consistently, when cultured microglia were polarized toward a pro-inflammatory phenotype with conditioned medium collected from neurons that had been subjected to oxygen-glucose deprivation (OGD neuron CM), they displayed reduced CBS expression and H 2 S production. Enhancing H 2 S bioavailability either by overexpressing CBS or by supplementing with exogenous H 2 S donors promoted a shift in microglial polarization from ischemia-induced pro-inflammatory phenotypes toward anti-inflammatory phenotypes. Mechanistically, microglia that were exposed to OGD neuron CM displayed reduced activation of AMP-activated protein kinase (AMPK), which was rescued by overexpressing CBS or by supplementing with H 2 S donors. Moreover, the promoting effects of H 2 S donors on microglial anti-inflammatory polarization were abolished by an AMPK inhibitor or CaMKKβ inhibitor. Our results suggested that reduced CBS-H 2 S-AMPK cascade activity contributed to microglia-mediated neuroinflammation following stroke. Targeting the CBS-H 2 S pathway is a promising therapeutic approach for ischemic stroke. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 08891591
- Volume :
- 66
- Database :
- Academic Search Index
- Journal :
- Brain, Behavior & Immunity
- Publication Type :
- Academic Journal
- Accession number :
- 125782262
- Full Text :
- https://doi.org/10.1016/j.bbi.2017.07.156