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Updated: May 3, 2026
Inducing Acute Lung Injury in Mice by Direct Intratracheal Lipopolysaccharide Instillation
Published on: July 6, 2019
[Protective effect of NMDA receptor antagonist memantine on acute lung injury in mice]
Ling Ma1, Wei Liu, Dandan Feng
1Department of Physiology, Xiangya School of Basic Medicine, Central South University, Changsha 410078; Yongzhou Vocational and Technical College, Yongzhou Hunan 425000, China).
Objective:
To investigate the protective effect of a non-specific NMDA receptor antagonist memantine on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice.
Methods:
Healthy male mice were divided into 4 groups: a normal group, a memantine group, an ALI group and a memantine+ALI group. The ALI group was induced by intraperitoneal injection of LPS (10 mg/kg). Memantine (10 mg/kg) was injected intraperitoneally before the injection of LPS to determine the effect of blockade of NMDA receptor in the memantine+ALI group. The lung wet/dry ratio was detected. HE staining was preformed to show the morphological changes in the lung tissue. Myeloperoxidase enzyme (MPO) activity and malondialdehyde (MDA) content in the lung tissue were detected. ELISA was used to detect the tumor necrosis factor-α (TNF-α) content and lactate dehydrogenase (LDH) activity in the bronchoalveolar lavage fluid (BALF).
Results:
Memantine pretreatment improved the LPS-induced ALI lung tissue morphological changes, reduced their lung wet/dry ratio, the levels of TNF-α and LDH activity in BALF, and also reduced the MPO and MDA content in the lung tissue.
Conclusion:
Blockade of NMDA receptors can ameliorate LPS-induced mice ALI.
Insights
Memantine, an NMDA receptor antagonist, protected mice against acute lung injury (ALI) induced by lipopolysaccharide (LPS). This treatment reduced lung damage and inflammation markers, suggesting a therapeutic potential for ALI.
Area of Science:
- Pharmacology
- Pulmonology
- Immunology
Background:
- Acute Lung Injury (ALI) is a severe inflammatory condition with limited treatment options.
- Lipopolysaccharide (LPS) is a potent inducer of ALI, commonly used in animal models.
- N-methyl-D-aspartate (NMDA) receptors play a role in inflammatory processes.
Purpose of the Study:
- To evaluate the protective effects of memantine, a non-specific NMDA receptor antagonist, against LPS-induced ALI in mice.
- To investigate the therapeutic potential of NMDA receptor blockade in mitigating lung injury.
Main Methods:
- Male mice were assigned to normal, memantine, ALI, and memantine+ALI groups.
- ALI was induced via intraperitoneal injection of LPS (10 mg/kg).
- Memantine (10 mg/kg) was administered prior to LPS challenge. Lung wet/dry ratio, histological changes (HE staining), myeloperoxidase (MPO) activity, malondialdehyde (MDA) content, tumor necrosis factor-alpha (TNF-α) levels, and lactate dehydrogenase (LDH) activity were assessed.
Main Results:
- Memantine pretreatment significantly attenuated LPS-induced lung tissue damage.
- Reduced lung wet/dry ratio and decreased MPO and MDA levels were observed in memantine-treated mice.
- Levels of inflammatory markers, including TNF-α and LDH activity in bronchoalveolar lavage fluid (BALF), were significantly lowered by memantine.
Conclusions:
- NMDA receptor blockade with memantine demonstrates a protective effect against LPS-induced ALI in a mouse model.
- Memantine ameliorates lung injury by reducing inflammation and oxidative stress.
- These findings suggest that targeting NMDA receptors could be a viable therapeutic strategy for ALI.
