Icariin enhances remyelination process after acute demyelination induced by cuprizone exposure.
Pathology are still progressive and cumulative in the remission course of relapsing-remitting MS (RRMS), thus drug treatment during the remission period may play a great role for the regeneration of the myelin sheath. C57BL/6 mice were fed with cuprizone (CPZ, 0.2% w/w) for 5 weeks to induce acute demyelination and oligodendrocytes degeneration, after which CPZ was withdrawn to allow recovery. Icariin (ICA, 6.25, 12.5 and 25mg/kg/day), vehicle (0.5% sodium carboxymethyl cellulose solution) or water was administrated orally to mice for 1 week after CPZ withdrawal. Luxol-fast blue (LFB), immunohistochemical or immunofluorescence staining was used to detect morphological and biological changes in the brains. CPZ administration for 5 weeks resulted in completely demyelination and remyelination occurred when CPZ was withdrawn. ICA treatment during the recovery period for 1 week significantly improved myelin restoration, enhanced NF200-positive axons repair, increased the number of APC+/Olig2+mature oligodendrocytes and prevented neuron-derived neurotrophic factor such as nerve growth factor (NGF) loss. Our results demonstrated that ICA treatment during the recovery period promotes remyelination and axon rewrapped, at least, in part, by promoting oligodendrogenesis and neurotrophic factor production.
Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, No. 45 Changchun Street, 100053 Beijing, PR China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, No. 12 Jichang Road, 510405 Guangzhou, PR China.
Yifan
Y
Zhang
Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, No. 45 Changchun Street, 100053 Beijing, PR China. Electronic address: yinll913@126.com.
Linlin
L
Yin
Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, No. 45 Changchun Street, 100053 Beijing, PR China; Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, No. 12 Jichang Road, 510405 Guangzhou, PR China.
Na
N
Zheng
Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, No. 45 Changchun Street, 100053 Beijing, PR China.
Li
L
Zhang
Xuan Wu Hospital of Capital Medical University, Beijing Geriatric Medical Research Center, Key Laboratory for Neurodegenerative Diseases of Ministry of Education, No. 45 Changchun Street, 100053 Beijing, PR China.
Jianghong
J
Liu
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, No. 12 Jichang Road, 510405 Guangzhou, PR China.
Weixiong
W
Liang
Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, No. 12 Jichang Road, 510405 Guangzhou, PR China. Electronic address: wqitcm@qq.com.
Qi
Q
Wang
D000818:Animals; D001369:Axons / Q000187:drug effects / Q000473:pathology; D001921:Brain / Q000187:drug effects* / Q000473:pathology*; D003471:Cuprizone / Q000008:administration & dosage; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000473:pathology* / Q000517:prevention & control; D005260:Female; D005419:Flavonoids / Q000008:administration & dosage*; D005625:Frontal Lobe / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D020932:Nerve Growth Factor / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology; D000074586:Remyelination / Q000187:drug effects*
D005419:Flavonoids; D003471:Cuprizone; D020932:Nerve Growth Factor; C056599:icariin
Cuprizone; Demyelination; Multiple sclerosis; Myelin; Oligodendrogenesis