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Hydroxyfasudil ameliorates experimental autoimmune encephalomyelitis possibly through immunomodulation and anti-inflammatory effects
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Abstracts / Journal of the Neurological Sciences 405S (2019) 116535
WCN19-0043 Journal of the Neurological Sciences 405S (2019) 103979 Free papers 12 - MS & demyelinating Comparison of brain volume between neuromyelitis optic and multiple sclerosis patients in Indonesia R. Estiasaria, S. Firdausiaa, R. Mulyadib, R. Eddy Yunusb a Faculty of Medicine Universitas Indonesia, Neurology, Jakarta, Indonesia ^ b Faculty of Medicine Universitas Indonesia, Radiology, Jakarta, Indonesia Introduction Brain atrophy in Multiple Sclerosis(MS) has already well known which reflect axon loss and progression of the disease. However, study in Neuromyelitis Optic(NMO) brain volume (BV) is not as much as MS. This study aims to compare the BV between NMO and MS group and to analyze the association with disease severity, duration of illness and relapse-rate. Methods This is a cross-sectional study. Ten MS and NMO subjects, 18–65years-old participated in this study by giving written consent. The exclusion criteria, having neurological disorder other than MS/NMO and MRI procedure contraindicated. MS, NMO, and healthy control (HC) were matched based on age and sex. All subjects underwent brain MRI and the BV measured using Freesurfer6.0. All procedure had been approved by Universitas Indonesia and Cipto-Mangunkusumo-Hospital Ethics Committee. Results No differences in age and sex between all groups. MS BV was smaller compared to HC in all part and also smaller from NMO groups except optic chiasma volume(OCV). NMO subjects have the smallest OCV (vs. HC p = .002, vs. MS p = .02). Another part of NMO BV was not significantly different from HC. A significant negative correlation was found between EDSS and corpus-callosal volume in MS and with greymatter volume in NMO. Duration of illness negatively correlated with white-matter volume in NMO but not in MS. Relapse-rate was negatively correlated with brainstem volume in NMO. Conclusion Brain atrophy is prominent in MS but not in NMO except in OCV. EDSS is correlated with corpus-callosal volume in MS but in NMO correlated with grey matter volume. doi:10.1016/j.jns.2019.10.317
Sclerosis of State Administration of Traditional Chinese Medicine- and Scientific and Technological Innovation Team of Integrated Chinese and Western M, Jingzhong, China ^ c Shanxi Datong University, Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Datong, China ^ d General Hospital of Datong Coal Mining Group, Dept. of Neurosurgery, Datong, China ^ e Fudan University, Institute of Neurology, Huashan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Shanghai, China Background Rho kinase inhibitor Fasudil is effective in the treatment of EAE, but its narrow safety window, lower bioavailability limit the clinical use. Hydroxyfasudil, active metabolite of Fasudil in vivo, exhibits higher biological activity and longer half-period. Objective To observe the therapeutic potential of Hydroxyfasudil in EAE, and explore its possible mechanisms. Material and methods The effects of Hydroxyfasudil on cell viability. We further explored therapeutic effect in EAE model. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides (MOG35-55), which were divided into EAE group, Hydroxyfasudil group. Hydroxyfasudil was injected intraperitoneally (40 mg/kg/day) on day 3 post immunization. The injection of saline was set up as control in a similar manner. Results Hydroxyfasudil was well tolerant in vitro. Hydroxyfasudil delayed the clinical onset and suppressed the severity of EAE. Demyelination and cell infiltration in spinal cords of Hydroxyfasudil group were significantly decreased. Flow cytometry analysis showed that Hydroxyfasudil reduced CD4+IFN-γ+ and CD4+IL-17+ but increased CD4+CD25+ T cells. Hydroxyfasudil decreased inflammatory cytokine, chemokine and inhibited NF-κB, COX-2, iNOS. According to RTPCR analysis, Hydroxyfasudil suppressed iNOS, CD68 and TNF-α, while enhanced Arg-1, IL-4 and TGF-β. Conclusion Hydroxyfasudil should be a potential approach for EAE through immunomodulation, anti-inflammatory effects, the transformation of M1 type macrophages to M2, preventing the infiltration of inflammatory cells into CNS. (NNSF of China 81473577, Shanxi Scholarship Council of China 2014-7, 2011 Cultivation Project of Shanxi University of TCM 2011PY-1. Ma and Xiao are corresponding authors). Keywords: Hydroxyfasudil, Experimental autoimmune encephalomyelitis, Rho kinase inhibitor, Immunomodulation, M2 polarization
WCN19-0128 Journal of the Neurological Sciences 405S (2019) 103980
doi:10.1016/j.jns.2019.10.318
Free papers 12 - MS & demyelinating Hydroxyfasudil ameliorates experimental autoimmune encephalomyelitis possibly through immunomodulation and anti-inflammatory effects J. Wangab, Q. Miaob, R.X. Suib, L.J. Songb, Z. Chaib, J.Z. Yubc, Y.H. Lic, J.J. Huangbd, L. Fengc, B.G. Xiaoe, C.G. Maabc a Shanxi Medical University, Dept. of Neurology, Taiyuan, China ^ b Shanxi University of Chinese Medicine, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple
WCN19-0615 Journal of the Neurological Sciences 405S (2019) 103981 Free papers 12 - MS & demyelinating Multiple sclerosis and antiphospholipid antibodies: Clinical features and prognosis
Abstracts / Journal of the Neurological Sciences 405S (2019) 116535
WCN19-0043 Journal of the Neurological Sciences 405S (2019) 103979 Free papers 12 - MS & demyelinating Comparison of brain volume between neuromyelitis optic and multiple sclerosis patients in Indonesia R. Estiasaria, S. Firdausiaa, R. Mulyadib, R. Eddy Yunusb a Faculty of Medicine Universitas Indonesia, Neurology, Jakarta, Indonesia ^ b Faculty of Medicine Universitas Indonesia, Radiology, Jakarta, Indonesia Introduction Brain atrophy in Multiple Sclerosis(MS) has already well known which reflect axon loss and progression of the disease. However, study in Neuromyelitis Optic(NMO) brain volume (BV) is not as much as MS. This study aims to compare the BV between NMO and MS group and to analyze the association with disease severity, duration of illness and relapse-rate. Methods This is a cross-sectional study. Ten MS and NMO subjects, 18–65years-old participated in this study by giving written consent. The exclusion criteria, having neurological disorder other than MS/NMO and MRI procedure contraindicated. MS, NMO, and healthy control (HC) were matched based on age and sex. All subjects underwent brain MRI and the BV measured using Freesurfer6.0. All procedure had been approved by Universitas Indonesia and Cipto-Mangunkusumo-Hospital Ethics Committee. Results No differences in age and sex between all groups. MS BV was smaller compared to HC in all part and also smaller from NMO groups except optic chiasma volume(OCV). NMO subjects have the smallest OCV (vs. HC p = .002, vs. MS p = .02). Another part of NMO BV was not significantly different from HC. A significant negative correlation was found between EDSS and corpus-callosal volume in MS and with greymatter volume in NMO. Duration of illness negatively correlated with white-matter volume in NMO but not in MS. Relapse-rate was negatively correlated with brainstem volume in NMO. Conclusion Brain atrophy is prominent in MS but not in NMO except in OCV. EDSS is correlated with corpus-callosal volume in MS but in NMO correlated with grey matter volume. doi:10.1016/j.jns.2019.10.317
Sclerosis of State Administration of Traditional Chinese Medicine- and Scientific and Technological Innovation Team of Integrated Chinese and Western M, Jingzhong, China ^ c Shanxi Datong University, Institute of Brain Science, Shanxi Key Laboratory of Inflammatory Neurodegenerative Diseases, Datong, China ^ d General Hospital of Datong Coal Mining Group, Dept. of Neurosurgery, Datong, China ^ e Fudan University, Institute of Neurology, Huashan Hospital, Institutes of Brain Science, State Key Laboratory of Medical Neurobiology, Shanghai, China Background Rho kinase inhibitor Fasudil is effective in the treatment of EAE, but its narrow safety window, lower bioavailability limit the clinical use. Hydroxyfasudil, active metabolite of Fasudil in vivo, exhibits higher biological activity and longer half-period. Objective To observe the therapeutic potential of Hydroxyfasudil in EAE, and explore its possible mechanisms. Material and methods The effects of Hydroxyfasudil on cell viability. We further explored therapeutic effect in EAE model. Female C57BL/6 mice were immunized with myelin oligodendrocyte glycoprotein peptides (MOG35-55), which were divided into EAE group, Hydroxyfasudil group. Hydroxyfasudil was injected intraperitoneally (40 mg/kg/day) on day 3 post immunization. The injection of saline was set up as control in a similar manner. Results Hydroxyfasudil was well tolerant in vitro. Hydroxyfasudil delayed the clinical onset and suppressed the severity of EAE. Demyelination and cell infiltration in spinal cords of Hydroxyfasudil group were significantly decreased. Flow cytometry analysis showed that Hydroxyfasudil reduced CD4+IFN-γ+ and CD4+IL-17+ but increased CD4+CD25+ T cells. Hydroxyfasudil decreased inflammatory cytokine, chemokine and inhibited NF-κB, COX-2, iNOS. According to RTPCR analysis, Hydroxyfasudil suppressed iNOS, CD68 and TNF-α, while enhanced Arg-1, IL-4 and TGF-β. Conclusion Hydroxyfasudil should be a potential approach for EAE through immunomodulation, anti-inflammatory effects, the transformation of M1 type macrophages to M2, preventing the infiltration of inflammatory cells into CNS. (NNSF of China 81473577, Shanxi Scholarship Council of China 2014-7, 2011 Cultivation Project of Shanxi University of TCM 2011PY-1. Ma and Xiao are corresponding authors). Keywords: Hydroxyfasudil, Experimental autoimmune encephalomyelitis, Rho kinase inhibitor, Immunomodulation, M2 polarization
WCN19-0128 Journal of the Neurological Sciences 405S (2019) 103980
doi:10.1016/j.jns.2019.10.318
Free papers 12 - MS & demyelinating Hydroxyfasudil ameliorates experimental autoimmune encephalomyelitis possibly through immunomodulation and anti-inflammatory effects J. Wangab, Q. Miaob, R.X. Suib, L.J. Songb, Z. Chaib, J.Z. Yubc, Y.H. Lic, J.J. Huangbd, L. Fengc, B.G. Xiaoe, C.G. Maabc a Shanxi Medical University, Dept. of Neurology, Taiyuan, China ^ b Shanxi University of Chinese Medicine, The Key Research Laboratory of Benefiting Qi for Acting Blood Circulation Method to Treat Multiple
WCN19-0615 Journal of the Neurological Sciences 405S (2019) 103981 Free papers 12 - MS & demyelinating Multiple sclerosis and antiphospholipid antibodies: Clinical features and prognosis