title: Time-Dependent Progression of Demyelination and Axonal Pathology in MP4-Induced Experimental Autoimmune Encephalomyelitis.
abstract: BACKGROUND
  Multiple sclerosis (MS) is an autoimmune disease of the central nervous system (CNS) characterized by inflammation, demyelination and axonal pathology. Myelin basic protein/proteolipid protein (MBP-PLP) fusion protein MP4 is capable of inducing chronic experimental autoimmune encephalomyelitis (EAE) in susceptible mouse strains mirroring diverse histopathological and immunological hallmarks of MS. Lack of human tissue underscores the importance of animal models to study the pathology of MS.
  
  
  METHODS
  Twenty-two female C57BL/6 (B6) mice were immunized with MP4 and the clinical development of experimental autoimmune encephalomyelitis (EAE) was observed. Methylene blue-stained semi-thin and ultra-thin sections of the lumbar spinal cord were assessed at the peak of acute EAE, three months (chronic EAE) and six months after onset of EAE (long-term EAE). The extent of lesional area and inflammation were analyzed in semi-thin sections on a light microscopic level. The magnitude of demyelination and axonal damage were determined using electron microscopy. Emphasis was put on the ventrolateral tract (VLT) of the spinal cord.
  
  
  RESULTS
  B6 mice demonstrated increasing demyelination and severe axonal pathology in the course of MP4-induced EAE. Additionally, mitochondrial swelling and a decrease in the nearest neighbor neurofilament distance (NNND) as early signs of axonal damage were evident with the onset of EAE. In semi-thin sections we observed the maximum of lesional area in the chronic state of EAE while inflammation was found to a similar extent in acute and chronic EAE. In contrast to the well-established myelin oligodendrocyte glycoprotein (MOG) model, disease stages of MP4-induced EAE could not be distinguished by assessing the extent of parenchymal edema or the grade of inflammation.
  
  
  CONCLUSIONS
  Our results complement our previous ultrastructural studies of B6 EAE models and suggest that B6 mice immunized with different antigens constitute useful instruments to study the diverse histopathological aspects of MS.
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Johanna
authors.initials: J
authors.lastname: Prinz
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Aylin
authors.initials: A
authors.lastname: Karacivi
authors.affiliation: Department of Anatomy I, University of Cologne, Cologne, Germany.
authors.forename: Eva R
authors.initials: ER
authors.lastname: Stormanns
authors.affiliation: Department of Anatomy II, University of Cologne, Cologne, Germany.
authors.forename: Mascha S
authors.initials: MS
authors.lastname: Recks
authors.affiliation: Department of Anatomy and Cell Biology, University of Würzburg, Würzburg, Germany.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Kuerten
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology* / Q000648:ultrastructure; D003711:Demyelinating Diseases; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007114:Immunization; D008159:Lumbar Vertebrae / Q000473:pathology* / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D008867:Microtomy; D008928:Mitochondria / Q000473:pathology* / Q000648:ultrastructure; D008933:Mitochondrial Swelling; D009103:Multiple Sclerosis / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D004676:Myelin Basic Protein / Q000008:administration & dosage*; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage*; D009186:Myelin Sheath / Q000473:pathology* / Q000648:ultrastructure; D011993:Recombinant Fusion Proteins / Q000008:administration & dosage*; D012720:Severity of Illness Index; D013997:Time Factors
chemical_list: C101821:MP4 protein, chimeric; D004676:Myelin Basic Protein; D018991:Myelin Proteolipid Protein; D011993:Recombinant Fusion Proteins