Dexmedetomidine inhibits astrocyte pyroptosis and subsequently protects the brain in in vitro and in vivo models of sepsis.
Yi-Bing SunHailin ZhaoDong-Liang MuWenwen ZhangJiang CuiLingzhi WuAzeem AlamDong-Xin WangDaqing MaPublished in: Cell death & disease (2019)
Sepsis is life-threatening and often leads to acute brain damage. Dexmedetomidine, an α2-adrenoceptor agonist, has been reported to possess neuroprotective effects against various brain injury but underlying mechanisms remain elusive. In this study, in vitro and in vivo models of sepsis were used to explore the effects of dexmedetomidine on the inflammasome activity and its associated glia pyroptosis and neuronal death. In vitro, inflammasome activation and pyroptosis were found in astrocytes following lipopolysaccharide (LPS) exposure. Dexmedetomidine significantly alleviated astrocyte pyroptosis and inhibited histone release induced by LPS. In vivo, LPS treatment in rats promoted caspase-1 immunoreactivity in astrocytes and caused an increase in the release of pro-inflammatory cytokines of IL-1β and IL-18, resulting in neuronal injury, which was attenuated by dexmedetomidine; this neuroprotective effect was abolished by α2-adrenoceptor antagonist atipamezole. Dexmedetomidine significantly reduced the high mortality rate caused by LPS challenge. Our data demonstrated that dexmedetomidine may protect glia cells via reducing pyroptosis and subsequently protect neurons, all of which may preserve brain function and ultimately improve the outcome in sepsis.
Keyphrases
- cardiac surgery
- cerebral ischemia
- brain injury
- acute kidney injury
- inflammatory response
- nlrp inflammasome
- anti inflammatory
- intensive care unit
- subarachnoid hemorrhage
- septic shock
- white matter
- resting state
- blood brain barrier
- oxidative stress
- multiple sclerosis
- spinal cord
- dna methylation
- cell proliferation
- immune response
- spinal cord injury
- machine learning
- liver failure
- functional connectivity
- hepatitis b virus
- cell cycle arrest
- cardiovascular events
- acute respiratory distress syndrome
- deep learning
- combination therapy