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. 2014 Mar 13;8:73. doi: 10.3389/fncel.2014.00073

Table 1.

Advantages and disadvantages of different animal models available to study the broad spectrum of MS-relevant processes.

Induction Animal models Strength Limitation
Autoimmune EAE [induced by CNS tissue; myelin peptides (MBP, PLP, MOG); adoptive transfer of myelin reactive T cells]

  • -is the most frequently used model to study autoimmune encephalitis in the CNS

  • -mimics MS with respect to clinical symptoms and pathology

  • -there is a broad spectrum of EAE induction protocols, allowing to study different aspects of MS

  • -displays a relatively sensitive read-out system

  • -is mainly useful to test putative immunosuppressive and neuroprotective drugs, to study the behavior of different T cells subtypes, mechanisms of neuronal damage and loss, reactions of resident glial cells and their interplay with peripheral immune cells, to investigate the role of different molecular factors on T cells activation and to study BBB dysfunctions

  • -an artificially induced sensitisation to myelin compounds -typically requires an application of adjuvant to activate the innate immune system

  • -there is probably a different way of T cells priming as compared to MS

  • -high complexity due to involvement of different cell types

  • -high variety in susceptibility to EAE in dependence of strains, gender, species or even different animal colonies potentially leading to discrepancies in different EAE studies

  • -does not reflect aspects of progressive MS

  • -the assessment of remyelination is at least problematic since both de- and remyelination can proceed simultaneously

  • -unpredictable localisation of lesions that classically occur in the spinal cord
Viral-autoimmune Theiler's murine encephalomyelitis virus (TMEV); mouse hepatitis virus (MHV); Semliki Forest virus (SFV)

  • -supports the environmental compound (early infections) of MS aetiology

  • -allows to study the phenomenon of epitope spreading

  • -useful to study mechanisms of viral infection of neuronal and glial cells as well as a viral persistence

  • -useful to study immune-mediated and virus-triggered demyelination but also to test different regenerative, neuroprotective, and immunosuppressive therapeutics

  • -the assessment of remyelination is at least problematic since both de-and remyelination can proceed simultaneously

  • -some protocols require surgery

  • -TMEV is time consuming and can be induced only in mice

  • -C57BL/6 mice clear TMEV → difficulties in use genetically modified strains that are mostly development in the C57BL/6 background
Toxic Cuprizone (systemic oral application)

  • -well reproducible, established model

  • -predictable kinetics of de- and remyelination

  • -clear detection/evaluation system

  • -simple induction protocol

  • -de- and remyelination take place in different regions and in both white and gray matter following different spatial and temporal pattern

  • -can be induced in different rodents and strains

  • -available as an acute and chronic demyelination model

  • -useful to study remyelination and cellular behavior in the absence of peripheral immune cells

  • -an artificial way of demyelination induction due to an irreversible damage of mature oligodendrocytes via a toxin of unknown mode of action

  • -T, B cells independent → only of limited relevance for MS and the development of immunomodulating drugs

  • -BBB remains intact

  • -clinical symptoms only purely reflect MS; no good clinical read-out

  • -time consuming (acute model: 5–8 weeks; chronic: 12–16 weeks)

  • -not useful to study spinal cord demyelination since demyelination occurs only in the brain
Lysolecithin and Ethidium bromide (focal injection of a toxin)

  • -well reproducible, established model

  • -predictable kinetics of de- and remyelination

  • -well known lesion site can be induced in brain or spinal cord

  • -useful to study remyelination and cellular behavior

  • -useful to test putative immunosuppressive, neuroprotective, and especially regenerative agents

  • -an artificial way of demyelination induction due to an irreversible selective damage of myelin producing cells in the lysolecithin model. Ethidium bromide damages all nucleolus containing cells.

  • -T, B cells independent → only of limited relevance for MS

  • -tissue damage due to injection procedure

  • -high complexity and difficulties in the assessment of remyelination in the spinal cord since different myelinating cells are involved in the remyelination
Genetic Jimpy, Shiverer (shi), Rumpshaker mice

  • -consistency in myelination defects

  • -useful to study dysfunctions of myelination, neuronal and glial behavior

  • -non inflammatory models

  • -poor relevance for MS