Montelukast, a cysteinyl leukotriene receptor-1 antagonist, attenuates chronic brain injury after focal cerebral ischaemia in mice and rats

J Pharm Pharmacol. 2011 Apr;63(4):550-7. doi: 10.1111/j.2042-7158.2010.01238.x. Epub 2011 Mar 1.

Abstract

Objectives: Previously we demonstrated the neuroprotective effect of montelukast, a cysteinyl leukotriene receptor-1 (CysLT(1) ) antagonist, on acute brain injury after focal cerebral ischaemia in mice. In this study, we have determined its effect on chronic brain injury after focal cerebral ischaemia in mice and rats.

Methods: After transient focal cerebral ischaemia was induced by middle cerebral artery occlusion, montelukast was intraperitoneally injected in mice or orally administered to rats for five days. Behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss were determined to evaluate brain lesions.

Key findings: Montelukast (0.1 mg/kg) attenuated behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss in mice, which was similar to pranlukast, another CysLT(1) receptor antagonist. Oral montelukast (0.5 mg/kg) was effective in rats and was more effective than edaravone, a free radical scavenger.

Conclusion: Montelukast protected mice and rats against chronic brain injury after focal cerebral ischaemia, supporting the therapeutic potential of CysLT(1) receptor antagonists.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / administration & dosage
  • Acetates / pharmacology
  • Acetates / therapeutic use*
  • Administration, Oral
  • Animals
  • Antipyrine / analogs & derivatives*
  • Antipyrine / therapeutic use
  • Atrophy / prevention & control
  • Behavior, Animal / drug effects
  • Brain Injury, Chronic / complications
  • Brain Injury, Chronic / pathology*
  • Brain Injury, Chronic / prevention & control*
  • Chromones / therapeutic use
  • Cyclopropanes
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Edaravone
  • Free Radical Scavengers / therapeutic use
  • Infarction, Middle Cerebral Artery / drug therapy*
  • Infarction, Middle Cerebral Artery / pathology*
  • Injections, Intraperitoneal
  • Leukotriene Antagonists / pharmacology
  • Leukotriene Antagonists / therapeutic use
  • Male
  • Mice
  • Mice, Inbred ICR
  • Nerve Degeneration / drug therapy*
  • Quinolines / administration & dosage
  • Quinolines / pharmacology
  • Quinolines / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Sulfides

Substances

  • Acetates
  • Chromones
  • Cyclopropanes
  • Free Radical Scavengers
  • Leukotriene Antagonists
  • Quinolines
  • Sulfides
  • montelukast
  • Edaravone
  • Antipyrine
  • pranlukast