Neuroprotective Effect of a New Free Radical Scavenger HL-008 in an Ischemia-Reperfusion Injury Rat Model

Neuroscience. 2021 Jun 15:465:105-115. doi: 10.1016/j.neuroscience.2021.04.012. Epub 2021 Apr 27.

Abstract

Oxidative stress plays a critical role in cerebral ischemia-reperfusion injury. We have previously developed a powerful antioxidant, HL-008. This study aimed to investigate the neuroprotective function of HL-008. HL-008 efficacy in vitro and in vivo was evaluated using a PC-12 cell oxidative stress model induced by hydrogen peroxide and a rat model of middle cerebral artery occlusion, respectively. The MTT assay was used to analyze cell viability. 2,3,5-Triphenyltetrazolium chloride and Hematoxylin and Eosin staining, immunofluorescence, western blot, and proteomics were used to evaluate the infarction volume, brain tissue morphology, apoptosis, inflammation, and related pathways. Indicators related to oxidative levels were also detected. HL-008 significantly reduced the cerebral infarction volume induced by ischemia-reperfusion, improved the neurological score, alleviated oxidative stress and inflammation in the brain tissue, reduced glial cell activation, inhibited brain tissue apoptosis by influencing multiple signaling pathways, and had a neuroprotective effect. If HL-008 is successfully developed, it could significantly improve stroke patients' quality of life.

Keywords: antioxidant; ischemia–reperfusion injury; oxidative stress; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Brain Ischemia* / drug therapy
  • Free Radical Scavengers / pharmacology
  • Humans
  • Infarction, Middle Cerebral Artery / drug therapy
  • Neuroprotective Agents* / pharmacology
  • Oxidative Stress
  • Quality of Life
  • Rats
  • Reperfusion Injury* / drug therapy

Substances

  • Free Radical Scavengers
  • Neuroprotective Agents