title: Complement C5 in experimental autoimmune encephalomyelitis (EAE) facilitates remyelination and prevents gliosis.
abstract: 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.
authors.affiliation: Department of Pathology (Neuropathology), F140, Albert Einstein College of Medicine, 1300 Morris Park Avenue, Bronx, NY 10461, USA.
authors.forename: Susanna H
authors.initials: SH
authors.lastname: Weerth
authors.forename: Horea
authors.initials: H
authors.lastname: Rus
authors.forename: Moon L
authors.initials: ML
authors.lastname: Shin
authors.forename: Cedric S
authors.initials: CS
authors.lastname: Raine
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D001253:Astrocytes / Q000473:pathology; D015415:Biomarkers; D001921:Brain / Q000473:pathology / Q000648:ultrastructure; D015815:Cell Adhesion Molecules / Q000378:metabolism; D003182:Complement C5 / Q000172:deficiency / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D005911:Gliosis / Q000473:pathology / Q000517:prevention & control*; D006461:Hemolysis; D051379:Mice; D009186:Myelin Sheath; D009412:Nerve Fibers / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration; D013116:Spinal Cord / Q000473:pathology / Q000648:ultrastructure; D014945:Wound Healing
chemical_list: D015415:Biomarkers; D015815:Cell Adhesion Molecules; D003182:Complement C5; D012333:RNA, Messenger