NMDA Receptor Antagonist Attenuates Bleomycin-Induced Acute Lung Injury.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
Memantine mitigates oxidative stress, lung inflammatory response and acute lung injury in BLM challenged mice.
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Yang
Y
Li
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Yong
Y
Liu
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
XiangPing
X
Peng
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China; Xiangya Nursing School, Central South University, Changsha, Hunan, China.
Wei
W
Liu
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
FeiYan
F
Zhao
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
DanDan
D
Feng
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
JianZhong
J
Han
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
YanHong
Y
Huang
Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
SiWei
S
Luo
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
Lian
L
Li
Department of Pediatrics, Xiangya Hospital, Central South University, Changsha, Hunan, China.
Shao Jie
SJ
Yue
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
QingMei
Q
Cheng
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
XiaoTing
X
Huang
Department of Physiology, Xiangya School of Medicine, Central South University, Changsha, Hunan, China.
ZiQiang
Z
Luo
D055371:Acute Lung Injury / Q000139:chemically induced* / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000596:Amino Acids / Q000378:metabolism; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects*; D001761:Bleomycin / Q000009:adverse effects*; D001992:Bronchoalveolar Lavage Fluid; D039481:CD11b Antigen / Q000378:metabolism; D002199:Capillary Permeability; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D015259:Dopamine Agents / Q000494:pharmacology; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D008315:Malondialdehyde / Q000378:metabolism; D008559:Memantine / Q000494:pharmacology; D051379:Mice; D020556:Neutrophil Infiltration; D009504:Neutrophils / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
D000596:Amino Acids; D000903:Antibiotics, Antineoplastic; D039481:CD11b Antigen; D016207:Cytokines; D015259:Dopamine Agents; D016194:Receptors, N-Methyl-D-Aspartate; D001761:Bleomycin; D018698:Glutamic Acid; D008315:Malondialdehyde; D008559:Memantine