Fasudil, an Inhibitor of Rho-associated Coiled-coil Kinase, Improves Cognitive Impairments Induced by Smoke Exposure

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Oct 30

PMID 27791202

Citations 9

Authors

Deng Xueyang

Ma Zhanqiang

Ma Chunhua

Hao Kun

Affiliations

Soon will be listed here.

Abstract

The current study was designed to investigate the pathological changes in brain induced by smoke exposure, and explore whether fasudil could alleviate these impairments.Adult C57BL/6 mice were exposed to tobacco smoking for four months, and fasudil was treated from the third months. To investigate lung injuries, the immunohistochemistry of lung tissue, immune cell infiltrations, cytokine productions in bronchoalveolar lavage (BAL) fluid, and seurm inflammatory cytokines were evaluated. To investigate cognitive impairments, Morris water maze test, hippocampal inflammatory cytokines and Rho associated signaling pathways were evaluated.Our findings showed fasudil administration inhibited the inflitration of inflammatory cells (macrophages, neutrophils, and lymphocytes), suppressed the production of inflammatory cytokines both in the BAL fluid, serum, and hippocampus. Further, fasudil significantly improved the spatial learning and memory impairments and reduced the elevation of hippocampal inflammatory cytokines induced by tobacco smoking. Of note, expressions of RhoA, ROCK1, ROCK2, caspase-3, caspase-9, bax and the phosphorylation of NF-κBp65 were increased accompanying the smoke exposure-induced cognitive impairments, which were significantly inhibited by fasudil treatment as indicted in western blot and immunohistochemistry analysis.Our results showed that fasudil exhibited protective effects on smoke exposure induced cognitive deficits which might involve with the regulation of Rho/ROCK/NF-κB pathways. Further studies are warranted before clinical application of fasudil.

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