ONO-1078 reduces NMDA-induced brain injury and vascular cell adhesion molecule-1 expression in rats  

作　　者：Li-huiZHANG Er-qingWEI 

机构地区：[1]DepartmentofPharmacology,SchoolofMedicine,ZhejiangUniversity,Hangzhou310031//MedicalSchool,HangzhouNormalUniversity,Hangzhou310018,China [2]DepartmentofPharmacology,SchoolofMedicine,ZhejiangUniversity,Hangzhou310031

出　　处：《Acta Pharmacologica Sinica》2005年第4期435-440,共6页中国药理学报（英文版）

基　　金：Project supported by the National Natural Science Foundation of China(No 30271498).

摘　　要：Aim:To determine whether ONO-1078 (pranlukast),a potent cysteinyl leukotriene receptor 1 (CysLTI) antagonist,has an effect on N-methyl-D-aspartate (NMDA)- induced brain injury and vascular cell adhesion molecule-1 (VCAM-1) expres- sion 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 rain 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:CysLT_1 receptor antagonist ONO-1078 at tenufftes 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.Aim:To determine whether ONO-1078 (pranlukast),a potent cysteinyl leukotriene receptor 1 (CysLTI) antagonist,has an effect on N-methyl-D-aspartate (NMDA)- induced brain injury and vascular cell adhesion molecule-1 (VCAM-1) expres- sion 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 rain 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:CysLT_1 receptor antagonist ONO-1078 at tenufftes 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.

关 键 词：leukotriene antagonists PRANLUKAST N-METHYLASPARTATE vascular cell adhesion molecule-1 NEUROTOXICITY brain injuries 

分 类 号：R742[医药卫生—神经病学与精神病学]