Complement C5 in experimental autoimmune encephalomyelitis (EAE) facilitates remyelination and prevents gliosis

Am J Pathol. 2003 Sep;163(3):1069-80. doi: 10.1016/S0002-9440(10)63466-9.


Activation of the classical complement system is known to play a central role in autoimmune demyelination. We have analyzed the role of complement component C5 in experimental autoimmune encephalomyelitis (EAE) using C5-deficient (C5-d) and C5-sufficient (C5-s) mice. Both groups of mice displayed early onset EAE, a short recovery phase, and similar stable chronic courses. However, in contrast to the clinical similarities, marked differences were apparent by histopathology. During acute EAE in C5-d, a delay in inflammatory cell infiltration and tissue damage was observed along with restricted lesion areas, which in C5-s mice were more extensive and diffuse. More striking were the differences in chronic lesions. In C5-d mice, inflammatory demyelination and Wallerian degeneration were followed by axonal depletion and severe gliosis, while in C5-s, the same initial signs were followed by axonal sparing and extensive remyelination. In C5-d, immunohistochemistry and Western blotting showed an increase in glial fibrillary acidic protein and a decrease in neurofilament protein, proteolipid protein, and several pro-inflammatory markers. These results in the EAE model indicate that absence of C5 resulted in fiber loss and extensive scarring, whereas presence of C5-favored axonal survival and more efficient remyelination.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Animals, Outbred Strains
  • Astrocytes / pathology
  • Biomarkers
  • Brain / pathology
  • Brain / ultrastructure
  • Cell Adhesion Molecules / metabolism
  • Complement C5 / deficiency
  • Complement C5 / metabolism*
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Encephalomyelitis, Autoimmune, Experimental / physiopathology*
  • Female
  • Gliosis / pathology
  • Gliosis / prevention & control*
  • Hemolysis
  • Mice
  • Myelin Sheath*
  • Nerve Fibers / pathology
  • RNA, Messenger / metabolism
  • Regeneration*
  • Spinal Cord / pathology
  • Spinal Cord / ultrastructure
  • Wound Healing


  • Biomarkers
  • Cell Adhesion Molecules
  • Complement C5
  • RNA, Messenger