Cysteinyl leukotriene receptor 1 partially mediates brain cryoinjury in mice.
OBJECTIVE
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.


CONCLUSIONS
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.
Ding
Qian
Q
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310058, China.
Fang
San-hua
SH
Zhou
Yu
Y
Zhang
Li-hui
LH
Zhang
Wei-ping
WP
Chen
Zhong
Z
Wei
Er-qing
EQ
D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000378:metabolism / Q000473:pathology; D002867:Chromones / Q000494:pharmacology; D003080:Cold Temperature / Q000009:adverse effects*; D006801:Humans; D020024:Leukotriene Antagonists / Q000494:pharmacology; D008297:Male; D051379:Mice; D008911:Minocycline / Q000494:pharmacology; D020033:Protein Isoforms / Q000378:metabolism*; D018077:Receptors, Leukotriene / Q000378:metabolism*
D002867:Chromones; D020024:Leukotriene Antagonists; D020033:Protein Isoforms; D018077:Receptors, Leukotriene; D008911:Minocycline; C083169:leukotriene D4 receptor; C047681:pranlukast