Effect of Fasudil on remyelination following cuprizone-induced demyelination
Authors: Qiang Miao
Ruo-Xuan Sui
Qing Wang
Li-Juan Song
Cun-Gen Ma
Yan-Hua Li
Jing Wang
Bao-Guo Xiao
Jie-Zhong Yu
Journal: CNS Neuroscience & Therapeutics (2020)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Fasudil; Rho kinase; cuprizone-induced demyelination; remyelination.
Affiliations: Department of Neurology, First Affiliated Hospital, Shanxi Medical University, Taiyuan, China., The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple Sclerosis of State Administration of Traditional Chinese Medicine, Shanxi University of Traditional Chinese Medicine, Taiyuan, China., Institute of Brain Science, Shanxi Datong University, Datong, China., Institute of Neurology, Huashan Hospital, Institutes of Brain Science and State Key Laboratory of Medical Neurobiology, Fudan University, Shanghai, China.

Abstract:  Background: Multiple sclerosis is characterized by demyelination/remyelination, neuroinflammation, and neurodegeneration. Cuprizone (CPZ)-induced toxic demyelination is an experimental animal model commonly used to study demyelination and remyelination in the central nervous system. Fasudil is one of the most thoroughly studied Rho kinase inhibitors. Methods: Following CPZ exposure, the degree of demyelination in the brain of male C57BL/6 mice was assessed by Luxol fast blue, Black Gold II, myelin basic protein immunofluorescent staining, and Western blot. The effect of Fasudil on behavioral change was determined using elevated plus maze test and pole test. The possible mechanisms of Fasudil action were examined by immunohistochemistry, flow cytometry, ELISA, and dot blot. Results: Fasudil improved behavioral abnormalities, inhibited microglia-mediated neuroinflammation, and promoted astrocyte-derived nerve growth factor and ciliary neurotrophic factor, which should contribute to protection and regeneration of oligodendrocytes. In addition, Fasudil inhibited the production of myelin oligodendrocyte glycoprotein antibody and the infiltration of peripheral CD4+ T cells and CD68+ macrophages, which appears to be related to the integrity of the blood-brain barrier. Conclusion: These results provide evidence for the therapeutic potential of Fasudil in CPZ-induced demyelination. However, how Fasudil acts on microglia, astrocytes, and immune cells remains to be further explored. 

Retracted: Yes

PubPeer comments:
 This manuscript shows extensive overlap with: CNS Neurosci Ther. 2020 Jan; 26(1): 76u201389. Published online 2019 May 23. Clin Immunol. 2019 Apr;201:35-47. doi: 10.1016 j.clim.2019.01.006. Epub 2019 Jan 17. Hydroxyfasudil alleviates demyelination through the inhibition of MOG antibody and microglia activation in cuprizone mouse model. Wang J1, Sui RX2, Miao Q2, Wang Q2, Song LJ2, Yu JZ3, Li YH3, Xiao BG4, Ma CG5. Here is the comparison:      , 
 Dear Daubenya Zeyheri: In our experimental design, we arranged two compounds, but shared normal and model groups. We didn t replicate the normal control and model groups. Some tests of the two compounds were same, but some tests were different, so we could not compare them together. In the separate articles, we did share the data from the normal group and the model group. This may be caused by misunderstanding  in part . However, we consider that this should not affect every result from this article. We didn t plagiarize any other data or graphs from other studies and didn t publish the same results repeatedly. In principle, our drug intervention experiments will be repeated more than three times independently. Only when the results show the identical trend in three experiments and the error between batches is less than 20%, we will do data analysis, chart making and statistical analysis. Of course, it s not good to present the same picture in two articles. when the deviation between the experimental batches is more than 10%, we generally do not consider to put the experimental data from different batches together for analysis and statistics. According to the editor s suggestion, we can reanalyze the experimental data from another 2-3 batches and remake completely different figures. We have enough number of animals in each batch (generally 8-10 group). Of course, we can guarantee that this will not affect any results or conclusions on this article. At that time, we thought it would be a good strategy to reduce the number of animals without affecting the experimental principles and results. Because animal experimental guidelines require us to minimize the number of animals on the basis of scientific experiment. We sincerely hope that the editor will give us the opportunity to revise them. From now on, we will learn this lesson carefully and will never have similar problems again. Sincerely yours, Prof. Bao-Guo Xiao Jing Wang ,