The effects of propofol on mitochondrial dysfunction following focal cerebral ischemia-reperfusion in rats

Neuropharmacology. 2014 Feb;77:358-68. doi: 10.1016/j.neuropharm.2013.08.029. Epub 2013 Sep 10.

Abstract

Propofol has been shown to attenuate brain injury in experimental ischemia models, but few studies have focused on the direct effect of propofol on mitochondrial dysfunction. In this study, we observed the effects of propofol on multiple aspects of mitochondrial dysfunction by studying the mitochondria isolated from rat brains subjected to focal cerebral ischemia-reperfusion. The mitochondria of the cortical tissue were isolated by the Percoll density gradient centrifugation. The isolated mitochondria were fixed and examined with electron microscopy. The calcium-induced mitochondrial swelling was quantified by measuring the decrease in light transmission at 540 nm with a spectrometer. Fluorescent probes were used to selectively stain mitochondria. Flow cytometry was used to measure the membrane potential and the production of reactive oxidative species. Propofol improved the signs of injury in the cortical mitochondria that were exposed to reperfusion following 2 h of focal ischemia. Propofol prevented calcium-induced mitochondrial swelling in a concentration-dependent manner. It did not affect the reperfusion-induced reduction in mitochondrial membrane potential. However, it decreased the production of the mitochondrial reactive oxidative species, which are generated during reperfusion. These results demonstrate that propofol may protect against mitochondrial dysfunction by preventing the ultrastructural change to the mitochondria and the calcium-induced mitochondrial swelling. This protective effect may be mediated by inhibiting the mitochondrial membrane permeability transition and reducing the production of reactive oxidative species in mitochondria.

Keywords: Focal cerebral ischemia; IB; MCAO; MMP; MPT; Mitochondrial membrane potential; OGD; Propofol; ROS; Reactive oxygen species; Reperfusion; Swelling; isolation buffer; mPTP; membrane permeability transition; middle cerebral artery occlusion; mitochondrial membrane potential; mitochondrial permeability transition pore; oxygen–glucose deprivation; reactive oxidative species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Ischemia / drug therapy*
  • Brain Ischemia / metabolism
  • Cerebral Cortex / drug effects
  • Cerebral Cortex / metabolism
  • Male
  • Membrane Potential, Mitochondrial / drug effects
  • Mitochondria / drug effects*
  • Mitochondria / metabolism
  • Neuroprotective Agents / pharmacology*
  • Neuroprotective Agents / therapeutic use
  • Propofol / pharmacology*
  • Propofol / therapeutic use
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species / metabolism
  • Reperfusion Injury / drug therapy*
  • Reperfusion Injury / metabolism

Substances

  • Neuroprotective Agents
  • Reactive Oxygen Species
  • Propofol