Targeting Smox Is Neuroprotective and Ameliorates Brain Inflammation in Cerebral Ischemia/Reperfusion Rats

Toxicol Sci. 2019 Apr 1;168(2):381-393. doi: 10.1093/toxsci/kfy300.

Abstract

Spermine oxidase (Smox) is a member of the polyamine oxidases and has been demonstrated to be involved in ischemic brain damage. In this study, we found that Smox expression was increased in a rat middle cerebral artery occlusion (MCAO) model and in cultured primary neurons after oxygen-glucose deprivation and reoxygenation (OGD/R). Smox downregulation by the adeno-associated virus RNA interference system significantly reduced the MCAO-induced brain infarct volume and neurological deficits and decreased neuronal apoptosis and inflammatory reactions. In addition, significant microglial activation and increased IL-6 and TNF-α expression were observed in microglia treated with supernatant from neurons after OGD/R. However, a significant reduction in microglial activation as well as IL-6 and TNF-α expression was observed in microglia treated with supernatant from Smox downregulated neurons after OGD/R. Therefore, the results indicated that Smox is an important mediator of cerebral ischemia injury and may be a therapeutic target for cerebral ischemia patients.

Keywords: cerebral ischemia; inflammation; neuron; spermine oxidase (Smox).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / genetics
  • Brain Ischemia / enzymology
  • Brain Ischemia / prevention & control*
  • Cells, Cultured
  • Disease Models, Animal
  • Down-Regulation
  • Encephalitis / enzymology
  • Encephalitis / prevention & control*
  • Infarction, Middle Cerebral Artery
  • Interleukin-6 / genetics
  • Male
  • Microglia / metabolism
  • Microglia / pathology
  • Neurons / metabolism
  • Neurons / pathology
  • Oxidoreductases Acting on CH-NH Group Donors / genetics*
  • Polyamine Oxidase
  • RNA, Small Interfering / genetics
  • Rats, Sprague-Dawley
  • Reperfusion Injury / enzymology
  • Reperfusion Injury / prevention & control*
  • Tumor Necrosis Factor-alpha / genetics

Substances

  • Interleukin-6
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha
  • Oxidoreductases Acting on CH-NH Group Donors