1-(2-4-dichlorobenzyl)indazole-3-carbohydrazide and Nervous-System-Diseases

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.

Topics: Analysis of Variance; Animals; Anti-Inflammatory Agents; Brain Edema; Brain Infarction; CD11b Antigen; Cell Line, Transformed; Cell Survival; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Interactions; Hydrazines; Indazoles; Infarction, Middle Cerebral Artery; Lipopolysaccharides; Male; Mice; Mice, Inbred ICR; Microglia; Nervous System Diseases; NF-kappa B; Psychomotor Performance; Signal Transduction; Time Factors