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Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair.
J Neurosci Methods 2017; 284:71-84JN

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.

OPTIMIZED METHOD

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.

COMPARISON WITH EXISTING METHOD(S)

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+Show Affiliations

Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA.Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA.Division of Biomedical Sciences, UCR School of Medicine, Riverside, CA 92521, USA.Department of Statistics, UCR-CNAS, Riverside, CA 92521, USA.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.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

28396177

Citation

Hasselmann, Jonathan P C., et al. "Consistent Induction of Chronic Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice for the Longitudinal Study of Pathology and Repair." Journal of Neuroscience Methods, vol. 284, 2017, pp. 71-84.
Hasselmann JPC, Karim H, Khalaj AJ, et al. Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair. J Neurosci Methods. 2017;284:71-84.
Hasselmann, J. P. C., Karim, H., Khalaj, A. J., Ghosh, S., & Tiwari-Woodruff, S. K. (2017). Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair. Journal of Neuroscience Methods, 284, pp. 71-84. doi:10.1016/j.jneumeth.2017.04.003.
Hasselmann JPC, et al. Consistent Induction of Chronic Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice for the Longitudinal Study of Pathology and Repair. J Neurosci Methods. 2017 Jun 1;284:71-84. PubMed PMID: 28396177.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Consistent induction of chronic experimental autoimmune encephalomyelitis in C57BL/6 mice for the longitudinal study of pathology and repair. AU - Hasselmann,Jonathan P C, AU - Karim,Hawra, AU - Khalaj,Anna J, AU - Ghosh,Subir, AU - Tiwari-Woodruff,Seema K, Y1 - 2017/04/08/ PY - 2016/12/10/received PY - 2017/03/15/revised PY - 2017/04/04/accepted PY - 2017/4/12/pubmed PY - 2018/3/10/medline PY - 2017/4/12/entrez KW - Autoimmune KW - Brain KW - Clinical score KW - Demyelination KW - Experimental autoimmune encephalomyelitis (EAE) KW - Immune cells KW - Immunohistochemistry KW - Infiltration KW - Inflammatory cells KW - MOG(35-55) KW - Mouse models of multiple sclerosis KW - Multiple sclerosis (MS) KW - Myelin basic protein KW - Neurodegeneration KW - Pertussis toxin KW - Spinal cord SP - 71 EP - 84 JF - Journal of neuroscience methods JO - J. Neurosci. Methods VL - 284 N2 - 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. OPTIMIZED METHOD: 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. COMPARISON WITH EXISTING METHOD(S): 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. SN - 1872-678X UR - https://www.unboundmedicine.com/medline/citation/28396177/Consistent_induction_of_chronic_experimental_autoimmune_encephalomyelitis_in_C57BL/6_mice_for_the_longitudinal_study_of_pathology_and_repair_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0165-0270(17)30094-8 DB - PRIME DP - Unbound Medicine ER -