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Idazoxan reduces blood-brain barrier damage during experimental autoimmune encephalomyelitis in mouse.
Wang, Xin-Shi; Fang, Hui-Lin; Chen, Yu; Liang, Shan-Shan; Zhu, Zhen-Guo; Zeng, Qing-Yi; Li, Jia; Xu, Hui-Qin; Shao, Bei; He, Jin-Cai; Hou, Sheng-Tao; Zheng, Rong-Yuan.
Afiliación
  • Wang XS; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Fang HL; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Chen Y; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Liang SS; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Zhu ZG; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Zeng QY; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Li J; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Xu HQ; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Shao B; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • He JC; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
  • Hou ST; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China; Department of Biology, South University of Science and Technology of China, 1088 Xueyuan Road, Nanshan District, Shenzhen, Guangdong Province 518055, PR China. Electroni
  • Zheng RY; Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China. Electronic address: zhengry2013@163.com.
Eur J Pharmacol ; 736: 70-6, 2014 Aug 05.
Article en En | MEDLINE | ID: mdl-24797785
We have previously shown that Idazoxan (IDA), an imidazoline 2 receptor ligand, is neuroprotective against spinal cord injury caused by experimental autoimmune encephalomyelitis (EAE) in mouse, an animal modal of multiple sclerosis (MS). However, the protective mechanism remains unclear. Here, we provided evidence to show that IDA confers neuroprotection through reduction in blood-brain barrier (BBB) damage. EAE was induced by immunizing C57 BL/6 mice with myelin oligodendrocyte glycoprotein35-55 amino acid peptide (MOG35-55). IDA was administrated for 14 days after MOG immunization at 2 mg/kg (i.p., bid). Significant reduction in BBB damage occurred in the IDA-treated group of mice compared with the saline-treated group, as evidenced by the reduction in Evan׳s blue content in the brain tissue and the reduced BBB tight junction damage viewed under a transmission electron microscope. Moreover, EAE-induced reductions in tight junction proteins (JAM-1, Occludin, Claudin-5 and ZO-1) were also significantly ameliorated in IDA-treated mice, all of which supported the notion that IDA reduced BBB damage. Interestingly, the expression levels of extracellular matrix metalloproteinase-9 (MMP-9) and the ratio of MMP-9 against tissue inhibitor of metalloproteinase-1 (TIMP-1), which is known to be associated with MS-induced BBB damage, were significantly reduced in IDA-treated group, lending further support to the hypothesis that IDA confers brain protection through reducing BBB damage. This study raised a possibility that IDA is a promising pro-drug for development against MS.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Fármacos Neuroprotectores / Idazoxan / Encefalomielitis Autoinmune Experimental / Antiinflamatorios Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos
Texto completo
Añadir a Mi BVS
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Fármacos Neuroprotectores / Idazoxan / Encefalomielitis Autoinmune Experimental / Antiinflamatorios Límite: Animals Idioma: En Revista: Eur J Pharmacol Año: 2014 Tipo del documento: Article Pais de publicación: Países Bajos