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Isolation of Cortical Microglia with Preserved Immunophenotype and Functionality From Murine Neonates
Published on: January 30, 2014
Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation
Jiaxiang Shao1, Tengyuan Liu, Qian Reuben Xie
1School of Biomedical Engineering and Med-X Research Institute, Shanghai Jiao Tong University, 1954 Huashan Road, Shanghai 200030, People's Republic of China.
Abstract:
Neuroinflammation caused by microglial activation plays a key role in ischemia, neurodegeneration and many other CNS diseases. In this study, we found that Adjudin, a potential non-hormonal male contraceptive, exhibits additional function to reduce the production of proinflammatory mediators. Adjudin significantly inhibited LPS-induced IL-6 release and IL-6, IL-1β, TNF-α expression in BV2 microglial cells. Furthermore, Adjudin exhibited anti-inflammatory properties by suppression of NF-κB p65 nuclear translocation and DNA binding activity as well as ERK MAPK phosphorylation. To determine the in vivo effect of Adjudin, we used a permanent middle cerebral artery occlusion (pMCAO) mouse model and found that Adjudin could reduce ischemia-induced CD11b expression, a marker of microglial activation. Furthermore, Adjudin treatment attenuated brain edema and neurological deficits after ischemia but did not reduce infarct volume. Thus, our data suggest that Adjudin may be useful for mitigating neuroinflammation.
Insights
Adjudin, a potential male contraceptive, effectively reduces neuroinflammation by inhibiting microglial activation and pro-inflammatory mediators. This compound shows promise in treating central nervous system diseases linked to inflammation.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Microglial activation drives neuroinflammation in CNS diseases like ischemia and neurodegeneration.
- Pro-inflammatory mediators released by activated microglia contribute to disease pathogenesis.
Purpose of the Study:
- To investigate the anti-inflammatory effects of Adjudin, a non-hormonal male contraceptive candidate.
- To determine Adjudin's impact on microglial activation and associated inflammatory pathways.
Main Methods:
- In vitro studies using BV2 microglial cells stimulated with LPS.
- In vivo studies utilizing a permanent middle cerebral artery occlusion (pMCAO) mouse model.
- Analysis of inflammatory mediator production, NF-κB and ERK MAPK signaling pathways, and microglial activation markers.
Main Results:
- Adjudin significantly inhibited LPS-induced IL-6 release and expression of IL-6, IL-1β, and TNF-α in BV2 cells.
- Adjudin suppressed NF-κB p65 nuclear translocation and DNA binding activity, and ERK MAPK phosphorylation.
- In vivo, Adjudin reduced ischemia-induced CD11b expression, brain edema, and neurological deficits in pMCAO mice, without altering infarct volume.
Conclusions:
- Adjudin demonstrates significant anti-inflammatory properties by modulating microglial activation and inflammatory signaling.
- Adjudin may serve as a therapeutic agent for mitigating neuroinflammation in CNS disorders.

