title: Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair.
abstract: BACKGROUND
  While many groups use experimental autoimmune encephalomyelitis (EAE) as a model to uncover therapeutic targets and understand the pathology underlying multiple sclerosis (MS), EAE protocol variability introduces discrepancies in central nervous system (CNS) pathogenesis and clinical disease, limiting the comparability between studies and slowing much-needed translational research.
  Here we describe a detailed, reliable protocol for chronic EAE induction in C57BL/6 mice utilizing two injections of myelin oligodendrocyte glycoprotein (35-55) peptide mixed with complete Freund's adjuvant and paired with pertussis toxin.
  
  
  RESULTS
  The active MOG35-55-EAE protocol presented here induces ascending paralysis in 80-100% of immunized mice. We observe: (1) consistent T cell immune activation, (2) robust CNS infiltration by peripheral immune cells, and (3) perivascular demyelinating lesions concurrent with axon damage in the spinal cord and various brain regions, including the optic nerve, cortex, hippocampus, internal capsule, and cerebellum.
  
  
  METHODS
  Lack of detailed protocols, combined with variability between laboratories, make EAE results difficult to compare and hinder the use of this model for therapeutic development. We provide the most detailed active MOG35-55-EAE protocol to date. With this protocol, we observe high disease incidence and a consistent, reliable disease course. The resulting pathology is MS-like and includes optic neuritis, perivascular mononuclear infiltration, CNS axon demyelination, and axon damage in both infiltrating lesions and otherwise normal-appearing white matter.
  
  
  CONCLUSIONS
  By providing a detailed active MOG35-55-EAE protocol that yields consistent and robust pathology, we aim to foster comparability between pre-clinical studies and facilitate the discovery of MS therapeutics.
authors.affiliation: Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA.
authors.forename: Jonathan P C
authors.initials: JPC
authors.lastname: Hasselmann
authors.affiliation: Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA.
authors.forename: Hawra
authors.initials: H
authors.lastname: Karim
authors.affiliation: Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA.
authors.forename: Anna J
authors.initials: AJ
authors.lastname: Khalaj
authors.affiliation: Department of Statistics, UCR-CNAS, Riverside, CA 92521, USA.
authors.forename: Subir
authors.initials: S
authors.lastname: Ghosh
authors.affiliation: Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA; Department of Neuroscience, UCR School of Medicine, Riverside, CA 92521, USA; Center for Glial-Neuronal Interactions, UCR School of Medicine, CA 92506, USA. Electronic address: seema.tiwari-woodruff@medsch.ucr.edu.
authors.forename: Seema K
authors.initials: SK
authors.lastname: Tiwari-Woodruff
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004338:Drug Combinations; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D005260:Female; D005620:Freund's Adjuvant; D006801:Humans; D008137:Longitudinal Studies; D051379:Mice; D008810:Mice, Inbred C57BL; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology*; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D016896:Treatment Outcome
chemical_list: D004338:Drug Combinations; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C526792:myelin oligodendrocyte glycoprotein (35-50), Ala(37)-; D005620:Freund's Adjuvant
keywords: Autoimmune; Brain; Clinical score; Demyelination; Experimental autoimmune encephalomyelitis (EAE); Immune cells; Immunohistochemistry; Infiltration; Inflammatory cells; MOG(35-55); Mouse models of multiple sclerosis; Multiple sclerosis (MS); Myelin basic protein; Neurodegeneration; Pertussis toxin; Spinal cord