Idazoxan reduces blood-brain barrier damage during experimental autoimmune encephalomyelitis in mouse.

Authors: 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 
Citation: Wang XS, etal., Eur J Pharmacol. 2014 Aug 5;736:70-6. doi: 10.1016/j.ejphar.2014.04.034. Epub 2014 May 2.
Pubmed: (View Article at PubMed) PMID:24797785
DOI: Full-text: DOI:10.1016/j.ejphar.2014.04.034

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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CRRD ID: 13204801
Created: 2017-07-19
Species: All species
Last Modified: 2017-07-19
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.