Effect of idazoxan on the tight junctions of blood-brain barrier in mouse experimental autoimmune encephalomyelitis

Abstract

Abstract: AIM: To study the effect of idazoxan(IDA)on the tight junctions of blood-brain barrier (BBB) in mouse experimental autoimmune encephalomyelitis (EAE) and the molecular mechanism.METHODS: Thirty six female C57BL/6 mice were randomly ascribed to control group, EAE group and IDA group, with 12 mice in each group. EAE was induced by MOG35-55. IDA (2 mg/kg, i.p., bid) was administrated for 15 days after MOG immunization. The signs of neurological defects of the mice were observed daily and scored, the pathological changes were observed, the BBB permeability were detected by Evan's blue extravasation, the ultrastructure of BBB were observed by transmission electron microscopy, and the expressions of BBB tight junction proteins (ZO-1,Claudin-5, Occludin, and JAM-1) in the brain of EAE mice were detected by Western blot analysis.RESULTS: Compared with EAE group, the score of neurological defects in IDA group was decreased, the pathological change and the ultrastrucuture of BBB destroy seen under the electron microscope was relieved, the BBB permeability was reduced, and the expressions of ZO-1 and Claudin-5 were increased (P<0.05).CONCLUSION: IDA possess neuroprotective effect on mouse EAE and ameliorate the dysfunction of BBB during EAE, whose effect might be related to the upregulation of the tight junction proteins ZO-1 and Claudin-5.

Key words: idazoxan, blood-brain barrier, tight junction, experimental autoimmune encephalomyelitis, mice

CLC Number:

R965.2

WANG Xin-shi, FANG Hui-lin, ZHU Zhen-guo, ZHU Pan, ZENG Qing-yi, ZHENG Rong-yuan. Effect of idazoxan on the tight junctions of blood-brain barrier in mouse experimental autoimmune encephalomyelitis[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2015, 20(2): 138-144.

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