Open AccessONO‐1078 reduces NMDA‐induced brain injury and vascular cell adhesion molecule‐1 expression in rats
Author(s) -
ZHANG Lihui,
WEI Erqing
Publication year - 2005
Publication title -
acta pharmacologica sinica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.514
H-Index - 90
eISSN - 1745-7254
pISSN - 1671-4083
DOI - 10.1111/j.1745-7254.2005.00063.x
Subject(s) - nmda receptor , microinjection , neuroprotection , pharmacology , neurotoxicity , antagonist , edaravone , edema , receptor antagonist , chemistry , medicine , anesthesia , receptor , endocrinology , toxicity
Aim : To determine whether ONO‐1078 (pranlukast), a potent cysteinyl leukotriene receptor 1 (CysLT 1 ) antagonist, has an effect on N‐methyl‐D‐aspartate (NMDA)‐induced brain injury and vascular cell adhesion molecule‐1 (VCAM‐1) expression in rats. Methods : Brain injury was induced by direct microinjection of NMDA (0.3 μmol in 1 μL of sterile 0.1 mol/L PBS, pH 7.4) into the cerebral cortex. The lesion volume (area), brain edema and neuron density were assessed by an image analyzer and the expression of VCAM‐1 in the cortex was detected by Western blot 24 h after NMDA injection. ONO‐1078 (0.03, 0.1, or 0.3 mg/kg) and edaravone (MCI‐186, 10 mg/kg), a neuroprotective agent, were ip injected 30 min before and after NMDA injection. Results : NMDA microinjection produced well‐defined focal lesions (Figure 1) dose‐and time‐dependently. ONO‐1078 (0.1, 0.3 mg/kg) and edaravone (10 mg/kg) decreased the total lesion volume, lesion area and brain edema induced by NMDA. Furthermore, ONO‐1078 (0.1, 0.3 mg/kg) significantly inhibited the enhanced expression of VCAM‐1 in the injured cortices, but edaravone did not have this effect. Conclusion : CysLT1 receptor antagonist ONO‐1078 attenuates NMDA‐induced brain damage in rats, and this might relate to the attenuation of NMDA receptor‐dependent neurotoxicity and the inhibition of the upregulation of VCAM‐1 expression.