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

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.

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“…Fasudil has a good therapeutic effect on EAN by attenuating Th1/Th17 cells and promoting Treg activation and M2 macrophage polarization. 61 …”

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“…The rats in each group were weighed and scored daily for 28 days. EAN clinical scores (Mausberg et al 2018;Zhao et al 2020;Szepanowski et al 2021) were graded as follows : 0 = normal; 1 = tail tension decrease; 2 = partial caudal paralysis; 3 = complete caudal palsy or without righting reflex; 4 = gait ataxia; 5 = mild hindlimb paralysis; 6 = moderate hindlimb paralysis; 7 = severe hindlimb paralysis; 8 = quadriplegia; 9 = dying; 10 = death.…”