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.
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.
Authors: Chelsea E Corser-Jensen; Dayton J Goodell; Ronald K Freund; Predrag Serbedzija; Robert C Murphy; Santiago E Farias; Mark L Dell'Acqua; Lauren C Frey; Natalie Serkova; Kim A Heidenreich Journal: Exp Neurol Date: 2014-03-25 Impact factor: 5.330