Hyperbaric oxygen enlarges the area of brain damage in MCAO rats by blocking autophagy via ERK1/2 activation

Eur J Pharmacol. 2014 Apr 5:728:93-9. doi: 10.1016/j.ejphar.2014.01.066. Epub 2014 Feb 7.

Abstract

Hyperbaric oxygen (HBO) is emerging as a therapy for brain ischemia, although its benefits are still debated. The present study aimed to investigate the effect of HBO on brain damage in a rat model of transient focal cerebral ischemia and its underlying mechanism of action. Male Wistar rats, which had suffered 1.5h of transient middle cerebral artery occlusion (tMCAO) and had a Longa's neuron score of 3, were given pure oxygen at 3.0 atm absolute, for 60 min after the third hour of reperfusion. After 24h of reperfusion, rat brains were removed and studied. 2,3,5-triphenyltetrazolium chloride (TTC) and hematoxylin and eosin staining revealed that the infarct ratio in the HBO group increased remarkably when compared with the MCAO group. Up-regulation of extracellular signal-regulated kinase 1/2 (ERK1/2) activation was detected in the HBO group because of reactive oxygen species (ROS) generation. Autophagy appeared to be obstructed in the HBO group. Administration of the ERK1/2 inhibitor U0126 decreased the infarct ratio and improved protein clearance by autophagy in the HBO group. Collectively, these results suggest that HBO enlarges the area of brain damage via reactive oxygen species-induced activation of ERK1/2, which interrupts autophagy flux.

Keywords: Autophagy; Extracellular signal-regulated kinase 1/2; Hyperbaric oxygen; Middle cerebral artery occlusion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / physiology*
  • Brain / enzymology
  • Brain / pathology*
  • Butadienes / pharmacology
  • Disease Models, Animal
  • Enzyme Inhibitors / pharmacology
  • Hyperbaric Oxygenation / adverse effects*
  • Hyperbaric Oxygenation / methods
  • Infarction, Middle Cerebral Artery / complications*
  • Ischemic Attack, Transient / enzymology
  • Ischemic Attack, Transient / etiology
  • Ischemic Attack, Transient / pathology
  • Ischemic Attack, Transient / therapy*
  • MAP Kinase Signaling System / physiology*
  • Male
  • Mitogen-Activated Protein Kinase 1 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 1 / genetics
  • Mitogen-Activated Protein Kinase 1 / metabolism
  • Mitogen-Activated Protein Kinase 3 / antagonists & inhibitors
  • Mitogen-Activated Protein Kinase 3 / genetics
  • Mitogen-Activated Protein Kinase 3 / metabolism
  • Nitriles / pharmacology
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Up-Regulation

Substances

  • Butadienes
  • Enzyme Inhibitors
  • Nitriles
  • Reactive Oxygen Species
  • U 0126
  • Mitogen-Activated Protein Kinase 1
  • Mitogen-Activated Protein Kinase 3