Inhibition of Nuclear Factor Kappa B: a Novel Therapeutic Target for Promoting Neuroregeneration in Alcoholic Encephalopathy

INTRODUCTION: The purpose of this study was to identify the effect of the Nuclear factor kappa B (NF-kappa B) inhibitor on the neuropsychiatric status and the state of the pool of nervous tissue progenitors in the brain of experimental animals with alcoholic encephalopathy (AE).
METHODS: The experiments were performed on C57BL/6 mice. The preservation of cognitive functions was studied using the “open field” test and the reproduction of the conditioned passive avoidance reflex (CPAR) of an electrical painful stimulus. Using in vitro cultural methods, we assessed the content and functional state of multipotent neural stem cells (SCs) and committed neuronal precursors (NPs) in the subventricular zone of the brain (SVZ), as well as the production of growth factors (active against neural progenitors) by different fractions of neuroglia.
RESULTS: We revealed a correction of disturbances in exploratory behavior and the level of reproducibility of CPAR in mice that were administered JSH-23 after modeling AE. These effects of restoration of cognitive functions developed against the background of a significant increase in the content of neuronal SCs and committed NPs in the SVZ (with a maximum of up to 152.6% and 211.1% (p < 0.05) of the level of similar values in untreated mice on the 7th day, respectively). At the same time, an increase in the proliferative activity and specialization intensity of progenitors of both types was recorded. They also revealed an increase in the production of growth fac-tors by oligodendrocytes in mice treated with an NF-kappa B blocker up to 174.3% and 190.8% (p < 0.05) of the control on days 3 and 7, respectively.
DISCUSSION AND CONCLUSION: These findings indicate the potential for the development of fundamentally new agents based on the NF-κB blocker JSH-23 for the treatment of AE. Their feature will be pronounced neuroregenerative activity. Such agents are not currently used in clinical settings.