Adjudin attenuates lipopolysaccharide (LPS)- and ischemia-induced microglial activation.

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.

• Authors: Jiaxiang Shao, Tengyuan Liu, Qian Reuben Xie, Tingting Zhang, Hemei Yu, Boshi Wang, Weihai Ying, Dolores D Mruk, Bruno Silvestrini, C Yan Cheng, Weiliang Xia
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 254 Issue 1-2 Pg. 83-90 (Jan 15 2013) ISSN: 1872-8421 [Electronic] Netherlands
• PMID: 23084372 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 Elsevier B.V. All rights reserved.

Chemical References

• 1-(2,4-dichlorobenzyl)indazole-3-carbohydrazide
• Anti-Inflammatory Agents
• CD11b Antigen
• Hydrazines
• Indazoles
• Lipopolysaccharides
• NF-kappa B

Topics

• Analysis of Variance
• Animals
• Anti-Inflammatory Agents (therapeutic use)
• Brain Edema (etiology, prevention & control)
• Brain Infarction (etiology, prevention & control)
• CD11b Antigen (metabolism)
• Cell Line, Transformed
• Cell Survival (drug effects)
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Interactions
• Hydrazines (therapeutic use)
• Indazoles (therapeutic use)
• Infarction, Middle Cerebral Artery (complications, drug therapy, pathology)
• Lipopolysaccharides (toxicity)
• Male
• Mice
• Mice, Inbred ICR
• Microglia (drug effects)
• NF-kappa B (metabolism)
• Nervous System Diseases (drug therapy, etiology)
• Psychomotor Performance (drug effects)
• Signal Transduction (drug effects)
• Time Factors