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Acta Pharmacologica Sinica 2005 Apr; 26 (4): 435-440; doi: 10.1111/j.1745-7254.2005.00063.x |
| Original Article | [ Full text ] |
| ONO-1078 reduces NMDA-induced brain injury and vascular cell adhesion molecule-1 expression in rats1 |
| Li-hui ZHANG2,3, Er-qing WEI2,4 2Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031; 3Medical School, Hangzhou Normal University, Hangzhou 310018, China |
Aim: To determine whether ONO-1078 (pranlukast),
a potent cysteinyl leukotriene receptor 1 (CysLT1)
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.
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Keywords: leukotriene antagonists; pranlukast; N-methylaspartate; vascular cell adhesion molecule-1; neurotoxicity; brain injuries |
| 1 Project supported by the National Natural Science Foundation of
China (No 30271498). 4 Correspondence to Prof Er-qing WEI. Phn 86-571-8721-7391. Fax 86-571-8721-7044. E-mail weieq2001@yahoo.com Received 2004-08-09 Accepted 2004-11-10 |
[ Full text ] |
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