Cysteinyl leukotriene receptor 1 partially mediates brain cryoinjury in mice

Acta Pharmacol Sin. 2007 Jul;28(7):945-52. doi: 10.1111/j.1745-7254.2007.00576.x.

Abstract

Aim: To determine whether the cysteinyl leukotriene receptor 1 (CysLT1 receptor) modulates brain cryoinjury and whether the CysLT1 receptor antagonist pranlukast exerts a time-dependent protective effect on cryoinjury in mice.

Methods: Brain cryoinjury was induced by applying a liquid nitrogen-cooled metal probe to the surface of the skull for 30 s. Brain lesion, neuron density, and endogenous IgG exudation were observed 24 h after cryoinjury. Transcription and the expression of the CysLT1 receptor were detected by RT-PCR and immunoblotting, and the localization of the receptor protein by double immunofluorescence.

Results: The mRNA and protein expressions of the CysLT1 receptor were upregulated in the brain 6-24 h after cryoinjury, and the CysLT1 receptor protein was primarily localized in the neurons, not in the astrocytes or microglia. Pre-injury treatments with multi-doses and a single dose of pranlukast (0.1 mg/kg) attenuated cryoinjury; postinjury single dose (0.1 mg/kg) at 30 min (not 1 h) after cryoinjury was also effective.

Conclusion: The CysLT1 receptor modulates cryoinjury in mice at least partly, and postinjury treatment with its antagonist pranlukast exerts the protective effect with a therapeutic window of 30 min.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain / pathology
  • Brain Injuries* / metabolism
  • Brain Injuries* / pathology
  • Chromones / pharmacology
  • Cold Temperature / adverse effects*
  • Humans
  • Leukotriene Antagonists / pharmacology
  • Male
  • Mice
  • Minocycline / pharmacology
  • Protein Isoforms / metabolism*
  • Receptors, Leukotriene / metabolism*

Substances

  • Chromones
  • Leukotriene Antagonists
  • Protein Isoforms
  • Receptors, Leukotriene
  • Minocycline
  • leukotriene D4 receptor
  • pranlukast