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Journal of Neuroimmune Pharmacology

, Volume 9, Issue 3, pp 399–412 | Cite as

An ανβ3 Integrin-Binding Peptide Ameliorates Symptoms of Chronic Progressive Experimental Autoimmune Encephalomyelitis by Alleviating Neuroinflammatory Responses in Mice

  • Fan Zhang
  • Jing Yang
  • Hong Jiang
  • Shu HanEmail author
ORIGINAL ARTICLE

Abstract

MOG35-55 triggers chronic, progressive experimental autoimmune encephalomyelitis (EAE) in C57BL/6 mice, and the clinical course of EAE in this model is characterized by macrophage infiltration, axonal demyelination/damage, and progressive paralysis. These stages are usually associated with inflammatory responses in the central nervous system (CNS). This study was designed to investigate the effects of C16, an ανβ3 integrin-binding peptide that targets integrins involved in the transendothelial migration of extravasating inflammatory cells. C16 was applied for only 2 weeks, but the benefits of this therapy lasted at least 8 weeks. Multiple histological and immunohistochemical staining studies, western blotting, enzyme-linked immunosorbent assays, electron microscopy, and cortical somatosensory-evoked potential (c-SEP) electrophysiological tests were employed to assess the degree of inflammation, axonal loss, white matter demyelination, neuronal apoptosis, extent of gliosis, expression of pro-inflammatory cytokines, and functional recovery of differently treated EAE model mice. The results showed that C16 treatment inhibited extensive leukocyte and macrophage accumulation and infiltration, reduced the expression of pro-inflammatory cytokines (tumor necrosis factor-α and interferon-γ), and thereby attenuated and delayed the progression of EAE. Moreover, astrogliosis, demyelination, and axonal and neuronal loss were all alleviated in C16-treated EAE animals, contributing to the improvement of function. These data suggest that the C16 peptide may act as a protective agent by reducing neuroinflammatory responses and improving the microenvironment.

Keywords

Multiple sclerosis Chronic, progressive experimental allergic encephalomyelitis Inflammatory cell infiltration Demyelination Neuroprotective effect 

Notes

Acknowledgments

This work was funded by the Zhejiang Provincial Natural Science Foundation of China no. R2110025 and the National Natural Science Foundation of China, project no. 81271333.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Supplementary material

11481_2014_9532_MOESM1_ESM.pdf (1.7 mb)
ESM 1 (PDF 1778 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Institute of Anatomy and Cell Biology, Medical CollegeZhejiang UniversityHangzhouChina
  2. 2.Department of Electrophysiology, Sir Run Run Shaw Hospital, Medical CollegeZhejiang UniversityHangzhouChina

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