TY - JOUR
T1 - The selective Rho-kinase inhibitor Fasudil is protective and therapeutic in experimental autoimmune encephalomyelitis
AU - Sun, Xiaojia
AU - Minohara, Motozumi
AU - Kikuchi, Hitoshi
AU - Ishizu, Takaaki
AU - Tanaka, Masahito
AU - Piao, Hua
AU - Osoegawa, Manabu
AU - Ohyagi, Yasumasa
AU - Shimokawa, Hiroaki
AU - Kira, Jun ichi
N1 - Funding Information:
This work was supported in part by grants from the Ministry of Education, Culture, Sports, Science and Technology of Japan, a Neuroimmunological Disease Research Committee grant from the Ministry of Health, Labour and Welfare of Japan for Research on Brain Science.
PY - 2006/11
Y1 - 2006/11
N2 - We studied the role of fasudil, a selective Rho-kinase inhibitor, in experimental autoimmune encephalomyelitis (EAE). Both parenteral and oral administration of fasudil prevented the development of EAE induced by proteolipid protein (PLP) p139-151 in SJL/J mice. Specific proliferation of lymphocytes to PLP was significantly reduced, together with a downregulation of interleukin (IL)-17 and a marked decrease of the IFN-γ/IL-4 ratio. Immunohistochemical examination also disclosed a marked decrease of inflammatory cell infiltration, and attenuated demyelination and acute axonal transaction. These results may provide a rationale of selective blockade of Rho-kinase by oral use of fasudil as a new therapy for multiple sclerosis.
AB - We studied the role of fasudil, a selective Rho-kinase inhibitor, in experimental autoimmune encephalomyelitis (EAE). Both parenteral and oral administration of fasudil prevented the development of EAE induced by proteolipid protein (PLP) p139-151 in SJL/J mice. Specific proliferation of lymphocytes to PLP was significantly reduced, together with a downregulation of interleukin (IL)-17 and a marked decrease of the IFN-γ/IL-4 ratio. Immunohistochemical examination also disclosed a marked decrease of inflammatory cell infiltration, and attenuated demyelination and acute axonal transaction. These results may provide a rationale of selective blockade of Rho-kinase by oral use of fasudil as a new therapy for multiple sclerosis.
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U2 - 10.1016/j.jneuroim.2006.06.027
DO - 10.1016/j.jneuroim.2006.06.027
M3 - Article
C2 - 16996142
AN - SCOPUS:33750618507
SN - 0165-5728
VL - 180
SP - 126
EP - 134
JO - Journal of Neuroimmunology
JF - Journal of Neuroimmunology
IS - 1-2
ER -