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


CONCLUSIONS
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.
Zhang
Li-hui
LH
Department of Pharmacology, School of Medicine, Zhejiang University, Hangzhou 310031, China.
Wei
Er-qing
EQ
D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives / Q000494:pharmacology; D001921:Brain / Q000473:pathology; D001930:Brain Injuries / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D002540:Cerebral Cortex / Q000378:metabolism*; D002867:Chromones / Q000494:pharmacology*; D000077553:Edaravone; D020024:Leukotriene Antagonists / Q000494:pharmacology*; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism*
D002867:Chromones; D020024:Leukotriene Antagonists; D018696:Neuroprotective Agents; D019010:Vascular Cell Adhesion Molecule-1; D016202:N-Methylaspartate; D000077553:Edaravone; D000983:Antipyrine; C047681:pranlukast