Pterostilbene Attenuates Astrocytic Inflammation and Neuronal Oxidative Injury After Ischemia-Reperfusion by Inhibiting NF-κB Phosphorylation

Front Immunol. 2019 Oct 17:10:2408. doi: 10.3389/fimmu.2019.02408. eCollection 2019.

Abstract

Astrocyte-mediated inflammation and oxidative stress elicit cerebral ischemia-reperfusion (IR) injury after stroke. Nuclear factor (NF)-κB activates astrocytes and generates pro-inflammatory factors. The purpose of the present study is to elucidate the effect of pterostilbene (PTE, a natural stilbene) on astrocytic inflammation and neuronal oxidative injury following cerebral ischemia-reperfusion injury. A middle cerebral artery occlusion-reperfusion (MCAO/R) mouse model and HT22/U251 co-culture model subjected to oxygen-glucose deprivation and re-introduction (OGD/R) were employed, with or without PTE treatment. The data showed that PTE delivery immediately after reperfusion, at 1 h after occlusion, decreased infarct volume, brain edema, and neuronal apoptosis and improved long-term neurological function. PTE decreased oxidation (i.e., production of reactive oxygen species, malondialdehyde) and inflammatory mediators (tumor necrosis factor-α, interleukin-1β, and interleukin-6) and increased anti-oxidative enzyme activities (i.e., of superoxide dismutase, glutathione peroxidase), by inhibiting phosphorylation and nuclear translocation of NF-κB. In conclusion, PTE attenuated astrocyte-mediated inflammation and oxidative injury following IR via NF-κB inhibition. Overall, PTE is a promising neuroprotective agent.

Keywords: astrocyte; cerebral ischemia-reperfusion injury; inflammation; nuclear factor-κB; oxidative stress; pterostilbene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / immunology
  • Astrocytes / immunology*
  • Astrocytes / pathology
  • Brain / immunology*
  • Brain / pathology
  • Inflammation / immunology
  • Inflammation / pathology
  • Inflammation / prevention & control
  • Inflammation Mediators / immunology
  • Male
  • Mice
  • NF-kappa B / immunology*
  • Neurons / immunology*
  • Neurons / pathology
  • Oxidation-Reduction
  • Phosphorylation / drug effects
  • Phosphorylation / immunology
  • Reperfusion Injury / immunology*
  • Reperfusion Injury / pathology
  • Reperfusion Injury / prevention & control
  • Stilbenes / pharmacology*

Substances

  • Inflammation Mediators
  • NF-kappa B
  • Stilbenes
  • pterostilbene