title: Idazoxan reduces blood-brain barrier damage during experimental autoimmune encephalomyelitis in mouse.
abstract: 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.
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Xin-Shi
authors.initials: XS
authors.lastname: Wang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Hui-Lin
authors.initials: HL
authors.lastname: Fang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Liang
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Zhen-Guo
authors.initials: ZG
authors.lastname: Zhu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Qing-Yi
authors.initials: QY
authors.lastname: Zeng
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Jia
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Hui-Qin
authors.initials: HQ
authors.lastname: Xu
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Bei
authors.initials: B
authors.lastname: Shao
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China.
authors.forename: Jin-Cai
authors.initials: JC
authors.lastname: He
authors.affiliation: 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. Electronic address: houshengtao@gmail.com.
authors.forename: Sheng-Tao
authors.initials: ST
authors.lastname: Hou
authors.affiliation: Department of Neurology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province 325000, PR China. Electronic address: zhengry2013@163.com.
authors.forename: Rong-Yuan
authors.initials: RY
authors.lastname: Zheng
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001522:Behavior, Animal / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D005260:Female; D019329:Idazoxan / Q000494:pharmacology / Q000627:therapeutic use*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000188:drug therapy; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D010539:Permeability / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D018696:Neuroprotective Agents; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse; D019329:Idazoxan
keywords: Blood–brain barrier; Experimental autoimmune encephalomyelitis; Idazoxan; Idazoxan (PubChem CID 54459); JAM-1; MMP-9; Tight junction