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ApoE-Deficient Promotes Blood–Brain Barrier Disruption in Experimental Autoimmune Encephalomyelitis via Alteration of MMP-9

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Abstract

Disruption of the blood–brain barrier (BBB) is a surrogate marker of acute inflammatory lesions in multiple sclerosis (MS) and its animal model experimental autoimmune encephalomyelitis (EAE). Data from experiments suggest that apolipoprotein E (ApoE) plays an important role in the antiinflammatory and immunological process in MS/EAE. Recent researches have shown that lack of ApoE leads to loss of cerebrovascular integrity and BBB breakdown causing neuronal injury. Cerebrovascular effects of ApoE might be another important element resulting to more susceptibility to MS/EAE. However, there is no direct evidence that ApoE dependently contributes to maintaining BBB integrity in EAE. In this study, we induced EAE in ApoE−/− mice and wild-type mice. During EAE, our results show that lack of ApoE increased the Evan’s blue (EB) permeability of BBB. Furthermore, deficiency of ApoE upregulated MMP-9 expression activity but decreased the expression of endothelial cell tight junction integral proteins claudin-5 and occludin. Our result also suggests that the protective role of ApoE in EAE by maintaining BBB integrity could be another interesting therapeutic target at MS/EAE.

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Acknowledgments

This work was supported partly by the National Research Program of China (81260188), partly by the Guangxi Higher Education research project grant (201204LX050), and partly by the Guangxi Natural Science Foundation Grants (0991009, 2012GXNSFAA053082).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital, Guangxi Medical University, Nanning, Guangxi, China

    Minghua Zheng, Yulan Tang, Chengcheng Yang, Yunfei Wei, Xiaoduan Yin & Qianqian Liu

  2. Department of Neurology, The People’s Hospital Of Guangxi Zhuang Autonomous Region, No 6, Shuangyong Road, Nanning, Guangxi, China

    Junjie Wei

Authors
  1. Minghua Zheng
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  2. Junjie Wei
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  3. Yulan Tang
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  4. Chengcheng Yang
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  5. Yunfei Wei
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  6. Xiaoduan Yin
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  7. Qianqian Liu
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Correspondence to Yulan Tang.

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M. Zheng and J. Wei contributed equally.

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Zheng, M., Wei, J., Tang, Y. et al. ApoE-Deficient Promotes Blood–Brain Barrier Disruption in Experimental Autoimmune Encephalomyelitis via Alteration of MMP-9. J Mol Neurosci 54, 282–290 (2014). https://doi.org/10.1007/s12031-014-0291-x

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  • DOI: https://doi.org/10.1007/s12031-014-0291-x

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