Hypothermia Attenuates Neuronal Damage via Inhibition of Microglial Activation, Including Suppression of Microglial Cytokine Production and Phagocytosis.
Tomoka KimuraKohki ToriuchiHiroki KakitaTetsuya TamuraSatoru TakeshitaYasumasa YamadaMineyoshi AoyamaPublished in: Cellular and molecular neurobiology (2020)
Although therapeutic hypothermia (TH) provides neuroprotection, the cellular mechanism underlying the neuroprotective effect of TH has not yet been fully elucidated. In the present study, we investigated the effect of TH on microglial activation to determine whether hypothermia attenuates neuronal damage via microglial activation. After lipopolysaccharide (LPS) stimulation, BV-2 microglia cells were cultured under normothermic (37 °C) or hypothermic (33.5 °C) conditions. Under hypothermic conditions, expression of pro-inflammatory cytokines and inducible nitric oxide synthase (iNOS) was suppressed. In addition, phagocytosis of latex beads was significantly suppressed in BV-2 cells under hypothermic conditions. Moreover, nuclear factor-κB signaling was inhibited under hypothermic conditions. Finally, neuronal damage was attenuated following LPS stimulation in neurons co-cultured with BV-2 cells under hypothermic conditions. In conclusion, hypothermia attenuates neuronal damage via inhibition of microglial activation, including microglial iNOS and pro-inflammatory cytokine expression and phagocytic activity. Investigating the mechanism of microglial activation regulation under hypothermic conditions could contribute to the development of novel neuroprotective therapies.
Keyphrases
- inflammatory response
- lps induced
- lipopolysaccharide induced
- induced apoptosis
- toll like receptor
- cerebral ischemia
- neuropathic pain
- nitric oxide synthase
- cardiac arrest
- brain injury
- oxidative stress
- nuclear factor
- cell cycle arrest
- poor prognosis
- nitric oxide
- spinal cord
- subarachnoid hemorrhage
- endothelial cells
- cell death
- cell proliferation
- signaling pathway
- mass spectrometry
- binding protein
- atomic force microscopy