Pterostilbene Attenuates Early Brain Injury Following Subarachnoid Hemorrhage via Inhibition of the NLRP3 Inflammasome and Nox2-Related Oxidative Stress

Mol Neurobiol. 2017 Oct;54(8):5928-5940. doi: 10.1007/s12035-016-0108-8. Epub 2016 Sep 24.

Abstract

Pterostilbene (PTE), one of the polyphenols present in plants such as blueberries and grapes, has been suggested to have various effects, such as anti-oxidation, anti-apoptosis, and anti-cancer effects. Subarachnoid hemorrhage (SAH) is a severe neurological event known for its high morbidity and mortality. Recently, early brain injury (EBI) has been reported to play a significant role in the prognosis of patients with SAH. The present study aimed to investigate whether PTE could attenuate EBI after SAH was induced in C57BL/6 J mice. We also studied possible underlying mechanisms. After PTE treatment, the neurological score and brain water content of the mice were assessed. Oxidative stress and neuronal injury were also evaluated. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activity was assessed using western blot analysis. Our results indicated that PTE treatment reduces the SAH grade, neurological score, and brain water content following SAH. PTE treatment also reduced NLRP3 inflammasome activation. PTE alleviated the oxidative stress following SAH as evidenced by the dihydroethidium staining, superoxide dismutase activity, malondialdehyde content, 3-nitrotyrosie and 8-hydroxy-2-deoxyguanosine levels, and gp91phox and 4-hydroxynonenal expression levels. Additionally, PTE treatment reduced neuronal apoptosis. In conclusion, our study suggests that PTE attenuates EBI following SAH possibly via the inhibition of NLRP3 inflammasome and Nox2-related oxidative stress.

Keywords: Early brain injury; NLRP3 inflammasome; Nox2; Oxidative stress; Pterostilbene; Subarachnoid hemorrhage.

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain Injuries / drug therapy*
  • Brain Injuries / metabolism
  • Inflammasomes / drug effects*
  • Inflammasomes / metabolism
  • Male
  • Mice, Inbred C57BL
  • NLR Family, Pyrin Domain-Containing 3 Protein / drug effects*
  • Oxidative Stress / drug effects
  • Stilbenes / pharmacology*
  • Subarachnoid Hemorrhage / drug therapy*
  • Subarachnoid Hemorrhage / metabolism

Substances

  • Inflammasomes
  • NLR Family, Pyrin Domain-Containing 3 Protein
  • Nlrp3 protein, mouse
  • Stilbenes
  • pterostilbene