Abstract
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.
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.
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References
Lee JM, Zipfel GJ, Choi DW . The changing landscape of ischaemic brain injury mechanisms. Nature 1999; 399: A7–14.
Dirnagl U, Simon RP, Hllenbeck JM . Ischemic tolerance and endogenous neuroprotection. Trends Neurosci 2003; 26: 248–54.
Zaremba J, Losy J . Adhesion molecules of immunoglobulin gene superfamily in stroke. Folia Morphol (Warsz) 2002; 61: 1–6.
Bitsch A, Klene W, Murtada L, Prange H, Rieckmann P . A longitudinal prospective study of soluble adhesion molecules in acute stroke. Stroke 1998; 29: 2129–35.
Stewart LR, White AR, Jobling MF, Needham BE, Maher F, Thyer J, et al. Involvement of the 5-lipoxygenase pathway in the neurotoxicity of the prion peptide PrP106–126. J Neurosci Res 2001; 65: 565–72.
Rao AM, Hatcher JF, Kindy MS, Dempsey RJ . Arachidonic acid and leukotriene C4: role in transient cerebral ischemia of gerbils. Neurochem Res 1999; 24: 1225–32.
Shishido Y, Furushiro M, Hashimoto S, Yokokura T . Effect of nordihydroguaiaretic acid on behavioral impairment and neuronal cell death after forebrain ischemia. Pharmacol Biochem Behav 2001; 69: 469–74.
Baskaya MK, Hu Y, Donaldson D, Maley M, Rao AM, Prasad MR, et al. Protective effect of the 5-lipoxygenase inhibitor AA-861 on cerebral edema after transient ischemia. J Neurosurg 1996; 85: 112–6.
Zhang WP, Wei EQ, Mei RH, Zhu CY, Zhao MH . Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia in rats. Acta Pharmacol Sin 2002; 23: 871–7.
Zeng LH, Zhang WP, Wang RD, Wang LP, Wei EQ . Protective effect of ONO-1078, a leukotriene antagonist, on focal cerebral ischemia in mice. Acta Pharm Sin 2001; 36: 148–50.
Zhang LH, Wei EQ . Time course of brain damage and expression of related molecules in rats with transient global cerebral ischemia. J Zhejiang Univ Med Sci 2002; 31: 77–80.
Zhang LH, Wei EQ . Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on transient global cerebral ischemia in rats. Acta Pharmacol Sin 2003; 24: 1241–7.
Toyoda K, Fujii K, Kamouchi M, Nakane H, Arihiro S, Okada Y, et al. Free radical scavenger, edaravone, in stroke with internal carotid artery occlusion. Neurol Sci 2004; 221: 11–7.
Yasuoka N, Nakajima W, Ishida A, Takada G . Neuroprotection of edaravone on hypoxic-ischemic brain injury in neonatal rats. Dev Brain Res 2004; 151: 129–39.
Iadecola C, Niwa K, Nogawa S, Zhao X, Nagayama M, Araki E, et al. Reduced susceptibility to ischemic brain injury and N-methyl-Daspartate-mediated neurotoxicity in cyclooxygenase-2-deficient mice. Proc Natl Acad Sci USA 2001; 98: 1294–9.
Kang H, Wei EQ, Yang XH, Zhang WP, Shen JZ . VCAM-1 expression, eosinophil infiltration, and pharmacological modulation in rat allergic airway inflammation. Acta Pharmacol Sin 2002; 23: 157–61.
Ciceri P, Rabuffetti M, Monopoli A, Nicosia S . Production of leukotrienes in a model of focal cerebral ischaemia in the rat. Br J Pharmacol 2001; 133: 1323–9.
Wallis RA, Panizzon KL . Protection from hypoxic and Nmethyl-D-aspartate injury with azelastine, a leukotriene inhibitor. Eur J Pharmacol 1993; 238: 165–71.
Block F, Loos M, Frohn C, Schwarz M . Association between inflammation and nigral neuronal damage following striatal excitotoxic lesion. Brain Res 2004; 998: 29–35.
Katayama T, Minami M, Nakamura M, Ito M, Katsuki H, Akaike A, et al. Excitotoxic injury induces production of monocyte chemoattractant protein-1 in rat cortico-striatal slice cultures. Neurosci Lett 2002; 328: 277–80.
Bouzioukh F, Tell F, Jean A, Rougon G . NMDA receptor and nitric oxide synthase activation regulate polysialylated neural cell adhesion molecule expression in adult brainstem synapses. J Neurosci 2001; 21: 4721–30.
Hoffman KB, Murray BA, Lynch G, Munirathinam S, Bahr BA . Delayed and isoform-specific effect of NMDA exposure on neural cell adhesion molecules in hippocampus. Neurosci Res 2001; 39: 167–73.
Blann A, Kumar P, Krupinski J, McCollum C, Beevers DG, Lip GY . Soluble intercelluar adhesion molecule-1, E-selectin, vascular cell adhesion molecule-1 and von Willebrand factor in stroke. Blood Coagul Fibrinolysis 1999; 10: 277–84.
Stanimirovic DB, Wong J, Shapiro A, Durkin JP . Increase in surface expression of ICAM-1, VCAM-1 and E-selectin in human cerebromicrovascular endothelial cells subjected to ischemia-like insults. Acta Neurochir Suppl (Wien) 1997; 70: 12–6.
James WG, Bullard DC, Hickey MJ . Critical role of the alpha 4 integrin/VCAM-1 pathway in cerebral leukocyte trafficking in lupusprone MRL/fas(lpr) mice. J Immunol 2003; 170: 520–7.
Laschinger M, Engelhardt B . Interaction of alpha4-integrin with VCAM-1 is involved in adhesion of encephalitogenic T cell blasts to brain endothelium but not in their transendothelial migration in vitro. J Neuroimmunol 2000; 102: 32–43.
Saito H, Shimizu H, Mita H, Maeda Y, Akiyama K . Histamine augments VCAM-1 expression on IL-4-and TNF-alpha-stimulated human umbilical vein endothelial cells. Int Arch Allergy Immunol 1996; 111: 126–32.
Yang XH, Wei EQ . Expression of vascular cell adhesion molecule-1 in lung slices from antigen sensitized rats and pharmacological modulation. J Zhejiang Univ Med Sci 2003; 32: 319–22.
Wu AY, Chik SC, Chen AW, Li Z, Tsang KW, Li W . Anti-inflammatory effects of high-dose montelukast in an animal model of acute asthma. Clin Exp Allergy 2003; 33: 359–66.
Abe S, Kirima K, Tsuchiya K, Okamoto M, Hasegawa T, Houchi H, et al. The reaction rate of edaravone (3-methyl-1-phenyl-2-pyrazolin-5-one (MCI-186)) with hydroxyl radical. Chem Pharm Bull (Tokyo) 2004; 52: 186–91.
Jiang MZ, Tsukahara H, Ohshima Y, Todoroki Y, Hiraoka M, Maeda M, et al. Effects of antioxidants and nitric oxide on TNF-alpha-induced adhesion molecule expression and NF-kappaB activation in human dermal microvascular endothelial cells. Life Sci 2004; 75: 1159–70.
Rajesh KG, Sasaguri S, Suzuki R, Maeda H . Antioxidant MCI-186 inhibits mitochondrial permeability transition pore and upregulates Bcl-2 expression. Am J Physiol Heart Circ Physiol 2003; 285: H2171–8.
Zhang XH, Matsuda N, Jesmin S, Sakuraya F, Gando S, Kemmotsu O, et al. Normalization by edaravone, a free radical scavenger, of irradiation-reduced endothelial nitric oxide synthase expression. Eur J Pharmacol 2003; 476: 131–7.
Qi X, Okuma Y, Hosoi T, Nomura Y . Edaravone protects against hypoxia/ischemia-induced endoplasmic reticulum dysfunction. J Pharmacol Exp Ther 2004; 311: 388–93.
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Project supported by the National Natural Science Foundation of China (No 30271498).
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Zhang, Lh., Wei, Eq. ONO-1078 reduces NMDA-induced brain injury and vascular cell adhesion molecule-1 expression in rats. Acta Pharmacol Sin 26, 435–440 (2005). https://doi.org/10.1111/j.1745-7254.2005.00063.x
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DOI: https://doi.org/10.1111/j.1745-7254.2005.00063.x