Effect of fasudil on experimental autoimmune neuritis and its mechanisms of action.

Yanyin Zhao,Baoguo Xiao,Bingyou Liu,Yi Wang

doi:10.1590/1414-431x20198669

Yanyin Zhao, Baoguo Xiao + Show 2 more

Open Access

https://doi.org/10.1590/1414-431x20198669

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Abstract

This study aimed to investigate the therapeutic effect of fasudil on treating experimental autoimmune neuritis (EAN). Twenty-four EAN mice were randomly assigned to fasudil treatment (Fasudil group) or saline treatment (EAN model group) for 28 days. Clinical symptom score was evaluated every other day; inflammatory cell infiltration, demyelination, anti-myelin basic protein (MBP), inflammatory cytokines, inducible nitric oxide synthase (iNOS), and arginase-1 were detected in sciatic nerves at day 28. Th1, Th2, Th17, and Tregs proportions in splenocytes were detected at day 28. Clinical symptom score was found to be attenuated in the Fasudil group compared to the EAN model group from day 12 to day 28. Sciatic nerve inflammatory cell counts by HE staining and demyelination by luxol fast blue staining were both reduced, while MBP was increased in the Fasudil group compared to the EAN model group at day 28. Interferon γ (IFN-γ) and interleukin (IL)-17 were reduced, while IL-4 and IL-10 were elevated in the Fasudil group at day 28. Sciatic nerve M1 macrophages marker iNOS was decreased while M2 macrophages marker arginase-1 was increased in the Fasudil group at day 28. CD4+IFN-γ+ (Th1) and CD4+IL-17+ (Th17) cell proportions were both decreased, CD4+IL-4+ (Th2) cell proportion was similar, while CD25+FOXP3+ (Treg) cell proportion in splenocytes was increased in the Fasudil group. In summary, fasudil presented a good therapeutic effect for treating EAN by attenuating Th1/Th17 cells and promoting Tregs activation as well as M2 macrophages polarization.

Highlights

Guillain-Barré syndrome (GBS), which is an autoimmune disease and an acute inflammatory disorder that afflicts the peripheral nervous system, is the most common and severe acute paralytic neuropathy, with approximately 100,000 persons developing this disease every year worldwide [1]
Establishment of experimental autoimmune neuritis (EAN) model Mice presented with apparent EAN symptoms from day 8 to 28 after immunization compared to mice without immunization, and exhibited elevated clinical symptoms scores from day 10 to 28 compared to mice without immunization
To measure antigen specific humoral immune response, serum anti-P0 peptide 180–199 immunoglobulin G (IgG) level was determined at day 28, which was greatly decreased in the Fasudil group compared with the EAN model group (Po0.001, Figure 4)

Summary

Introduction

Guillain-Barré syndrome (GBS), which is an autoimmune disease and an acute inflammatory disorder that afflicts the peripheral nervous system, is the most common and severe acute paralytic neuropathy, with approximately 100,000 persons developing this disease every year worldwide [1]. GBS pathological changes are commonly characterized by the loss of peripheral nerve myelin sheath and inflammatory cell infiltration, and it often presents with symmetrical weakness of limbs, numbness, and hyporeflexia [2,3]. As a selective RhoA/ROCK inhibitor, fasudil has been clinically applied for the treatment of subarachnoid hemorrhage since 1995, and has been administered to improve the cognitive decline in stroke patients [10,11]. A recent meta-analysis review observed that fasudil combined with methylcobalamin or lipoic acid promotes nerve conduction velocity in diabetic peripheral neuropathy patients [12]. The application of fasudil in treating GBS has not yet been explored

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