Remyelination in Animal Models of Multiple Sclerosis: Finding the Elusive Grail of Regeneration

Overview

Journal Front Mol Neurosci

Specialty Molecular Biology

Date 2023 Jul 14

PMID 37448959

Authors

Davin Packer

Emily E Fresenko

Em P Harrington

Affiliations

Soon will be listed here.

Abstract

Remyelination biology and the therapeutic potential of restoring myelin sheaths to prevent neurodegeneration and disability in multiple sclerosis (MS) has made considerable gains over the past decade with many regeneration strategies undergoing tested in MS clinical trials. Animal models used to investigate oligodendroglial responses and regeneration of myelin vary considerably in the mechanism of demyelination, involvement of inflammatory cells, neurodegeneration and capacity for remyelination. The investigation of remyelination in the context of aging and an inflammatory environment are of considerable interest for the potential translation to progressive multiple sclerosis. Here we review how remyelination is assessed in mouse models of demyelination, differences and advantages of these models, therapeutic strategies that have emerged and current pro-remyelination clinical trials.

Citing Articles

Oligodendrocytes, the Forgotten Target of Gene Therapy.

Ozgur-Gunes Y, Le Stunff C, Bougneres P Cells. 2024; 13(23).

PMID: 39682723 PMC: 11640421. DOI: 10.3390/cells13231973.

Oligodendroglial heterogeneity in health, disease, and recovery: deeper insights into myelin dynamics.

Serneels P, De Schutter J, De Groef L, Moons L, Bergmans S Neural Regen Res. 2024; 20(11):3179-3192.

PMID: 39665821 PMC: 11881716. DOI: 10.4103/NRR.NRR-D-24-00694.

A preclinical mice model of multiple sclerosis based on the toxin-induced double-site demyelination of callosal and cerebellar fibers.

Vejar S, Pizarro I, Pulgar-Sepulveda R, Vicencio S, Polit A, Amador C Biol Res. 2024; 57(1):48.

PMID: 39034395 PMC: 11265164. DOI: 10.1186/s40659-024-00529-7.

The interplay of inflammation and remyelination: rethinking MS treatment with a focus on oligodendrocyte progenitor cells.

Zveik O, Rechtman A, Ganz T, Vaknin-Dembinsky A Mol Neurodegener. 2024; 19(1):53.

PMID: 38997755 PMC: 11245841. DOI: 10.1186/s13024-024-00742-8.

References

Kutzelnigg A, Lucchinetti C, Stadelmann C, Bruck W, Rauschka H, Bergmann M . Cortical demyelination and diffuse white matter injury in multiple sclerosis. Brain. 2005; 128(Pt 11):2705-12. DOI: 10.1093/brain/awh641. View

Kim J, Budde M, Liang H, Klein R, Russell J, Cross A . Detecting axon damage in spinal cord from a mouse model of multiple sclerosis. Neurobiol Dis. 2005; 21(3):626-32. DOI: 10.1016/j.nbd.2005.09.009. View

Duncan G, Simkins T, Emery B . Neuron-Oligodendrocyte Interactions in the Structure and Integrity of Axons. Front Cell Dev Biol. 2021; 9:653101. PMC: 7982542. DOI: 10.3389/fcell.2021.653101. View

Hall S . The effect of injections of lysophosphatidyl choline into white matter of the adult mouse spinal cord. J Cell Sci. 1972; 10(2):535-46. DOI: 10.1242/jcs.10.2.535. View

Lindner M, Fokuhl J, Linsmeier F, Trebst C, Stangel M . Chronic toxic demyelination in the central nervous system leads to axonal damage despite remyelination. Neurosci Lett. 2009; 453(2):120-5. DOI: 10.1016/j.neulet.2009.02.004. View

Huseby E, Liggitt D, Brabb T, Schnabel B, Ohlen C, Goverman J . A pathogenic role for myelin-specific CD8(+) T cells in a model for multiple sclerosis. J Exp Med. 2001; 194(5):669-76. PMC: 2195947. DOI: 10.1084/jem.194.5.669. View

Rangachari M, Kuchroo V . Using EAE to better understand principles of immune function and autoimmune pathology. J Autoimmun. 2013; 45:31-9. PMC: 3963137. DOI: 10.1016/j.jaut.2013.06.008. View

Bieber A, Ure D, Rodriguez M . Genetically dominant spinal cord repair in a murine model of chronic progressive multiple sclerosis. J Neuropathol Exp Neurol. 2005; 64(1):46-57. DOI: 10.1093/jnen/64.1.46. View

Gonzalez G, Hofer M, Syed Y, Amaral A, Rundle J, Rahman S . Tamoxifen accelerates the repair of demyelinated lesions in the central nervous system. Sci Rep. 2016; 6:31599. PMC: 4995517. DOI: 10.1038/srep31599. View

10.

Cantoni C, Bollman B, Licastro D, Xie M, Mikesell R, Schmidt R . TREM2 regulates microglial cell activation in response to demyelination in vivo. Acta Neuropathol. 2015; 129(3):429-47. PMC: 4667728. DOI: 10.1007/s00401-015-1388-1. View

11.

Bender S, Weiss S . Pathogenesis of murine coronavirus in the central nervous system. J Neuroimmune Pharmacol. 2010; 5(3):336-54. PMC: 2914825. DOI: 10.1007/s11481-010-9202-2. View

12.

Paterson P . Transfer of allergic encephalomyelitis in rats by means of lymph node cells. J Exp Med. 1960; 111:119-36. PMC: 2137200. DOI: 10.1084/jem.111.1.119. View

13.

Rankin K, Mei F, Kim K, Shen Y, Mayoral S, Desponts C . Selective Estrogen Receptor Modulators Enhance CNS Remyelination Independent of Estrogen Receptors. J Neurosci. 2019; 39(12):2184-2194. PMC: 6433770. DOI: 10.1523/JNEUROSCI.1530-18.2019. View

14.

Call C, Bergles D . Cortical neurons exhibit diverse myelination patterns that scale between mouse brain regions and regenerate after demyelination. Nat Commun. 2021; 12(1):4767. PMC: 8346564. DOI: 10.1038/s41467-021-25035-2. View

15.

Blakemore W . Ethidium bromide induced demyelination in the spinal cord of the cat. Neuropathol Appl Neurobiol. 1982; 8(5):365-75. DOI: 10.1111/j.1365-2990.1982.tb00305.x. View

16.

Simons M, Nave K . Oligodendrocytes: Myelination and Axonal Support. Cold Spring Harb Perspect Biol. 2015; 8(1):a020479. PMC: 4691794. DOI: 10.1101/cshperspect.a020479. View

17.

Kotter M, Li W, Zhao C, Franklin R . Myelin impairs CNS remyelination by inhibiting oligodendrocyte precursor cell differentiation. J Neurosci. 2006; 26(1):328-32. PMC: 6674302. DOI: 10.1523/JNEUROSCI.2615-05.2006. View

18.

Wergeland S, Torkildsen O, Myhr K, Mork S, Bo L . The cuprizone model: regional heterogeneity of pathology. APMIS. 2012; 120(8):648-57. DOI: 10.1111/j.1600-0463.2012.02882.x. View

19.

Bunge M, Bunge R, RIS H . Ultrastructural study of remyelination in an experimental lesion in adult cat spinal cord. J Biophys Biochem Cytol. 1961; 10:67-94. PMC: 2225064. DOI: 10.1083/jcb.10.1.67. View

20.

El Waly B, Buttigieg E, Karakus C, Brustlein S, Debarbieux F . Longitudinal Intravital Microscopy Reveals Axon Degeneration Concomitant With Inflammatory Cell Infiltration in an LPC Model of Demyelination. Front Cell Neurosci. 2020; 14:165. PMC: 7324938. DOI: 10.3389/fncel.2020.00165. View