NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury

• Published in: PloS one Vol. 10; no. 5; p. e0125873
• Main Authors: Li, Yang, Liu, Yong, Peng, XiangPing, Liu, Wei, Zhao, FeiYan, Feng, DanDan, Han, JianZhong, Huang, YanHong, Luo, SiWei, Li, Lian, Yue, Shao Jie, Cheng, QingMei, Huang, XiaoTing, Luo, ZiQiang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.05.2015; Public Library of Science (PLoS)
• Subjects: Acute Lung Injury - chemically induced; Acute Lung Injury - drug therapy; Acute Lung Injury - metabolism; Acute Lung Injury - pathology; Amino Acids - metabolism; Animals; Antibiotics, Antineoplastic - adverse effects; Bleomycin; Bleomycin - adverse effects; Bronchoalveolar Lavage Fluid; Capillary Permeability; CD11b antigen; CD11b Antigen - metabolism; Cell activation; Central nervous system; Complications and side effects; Cytokines; Cytokines - metabolism; Disease Models, Animal; Dopamine Agents - pharmacology; Drug therapy; Edema; Female; Gene expression; Glutamic Acid - metabolism; Glutamic acid receptors (ionotropic); Health aspects; Hyperoxia; Infiltration; Inflammation; Inflammatory response; Injuries; Laboratory animals; Leukocytes; Leukocytes (neutrophilic); Lung diseases; Lungs; Malondialdehyde - metabolism; Medicine; Memantine; Memantine - pharmacology; Mice; N-methyl-D-aspartate; N-Methyl-D-aspartic acid receptors; Nervous system; Neurotoxicity; Neutrophil Infiltration; Neutrophils; Neutrophils - metabolism; Oxidative stress; Physiological aspects; Physiology; Pulmonary fibrosis; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Risk factors; Rodents; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0125873

Glutamate is a major neurotransmitter in the central nervous system (CNS). Large amount of glutamate can overstimulate N-methyl-D-aspartate receptor (NMDAR), causing neuronal injury and death. Recently, NMDAR has been reported to be found in the lungs. The aim of this study is to examine the effects of memantine, a NMDAR channel blocker, on bleomycin-induced lung injury mice. C57BL/6 mice were intratracheally injected with bleomycin (BLM) to induce lung injury. Mice were randomized to receive saline, memantine (Me), BLM, BLM plus Me. Lungs and BALF were harvested on day 3 or 7 for further evaluation. BLM caused leukocyte infiltration, pulmonary edema and increase in cytokines, and imposed significant oxidative stress (MDA as a marker) in lungs. Memantine significantly mitigated the oxidative stress, lung inflammatory response and acute lung injury caused by BLM. Moreover, activation of NMDAR enhances CD11b expression on neutrophils. Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice.