Although spontaneous remyelination does occur in multiple sclerosis lesions, its extent within the global population with this disease is presently unknown. We have systematically analysed the incidence and distribution of completely remyelinated lesions (so-called shadow plaques) or partially remyelinated lesions (shadow plaque areas) in 51 autopsies of patients with different clinical courses and disease durations. The extent of remyelination was variable between cases. In 20% of the patients, the extent of remyelination was extensive with 60-96% of the global lesion area remyelinated. Extensive remyelination was found not only in patients with relapsing multiple sclerosis, but also in a subset of patients with progressive disease. Older age at death and longer disease duration were associated with significantly more remyelinated lesions or lesion areas. No correlation was found between the extent of remyelination and either gender or age at disease onset. These results suggest that the variable and patient-dependent extent of remyelination must be considered in the design of future clinical trials aimed at promoting CNS repair.
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http://dx.doi.org/10.1093/brain/awl217 | DOI Listing |
eNeuro
January 2025
Graduate School of Pharmaceutical Science, Tokushima Bunri University, Sanuki 769-2193, Japan
Cuprizone (CPZ) is a widely used toxin that induces demyelinating diseases in animal models, producing multiple sclerosis (MS)-like pathology in rodents. CPZ is one of the few toxins that triggers demyelination and subsequent remyelination following the cessation of its application. This study examines the functional consequences of CPZ-induced demyelination and the subsequent recovery of neural communication within the anterior cingulate cortex (ACC), with a particular focus on interhemispheric connectivity via the corpus callosum (CC).
View Article and Find Full Text PDFBrain Res
December 2024
Institute of Anatomy, Rostock University Medical Center, Gertrudenstraße 9, Rostock 18057, Germany. Electronic address:
Multiple Sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Cuprizone-induced demyelination, wherein mice are fed a diet containing the copper chelator cuprizone, is a well-established model that replicates key features of demyelination and remyelination. However, the dose-response relationship of cuprizone is complex; high concentrations can induce toxicity, whereas low doses may fail to produce reliable demyelination across subjects.
View Article and Find Full Text PDFCNS Neurosci Ther
November 2024
Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, People's Republic of China.
Int J Mol Sci
October 2024
NeuroRepair Department, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland.
Pharmacol Rev
October 2024
Department of Immunology and Regenerative Biology, Weizmann Institute of Science, Rehovot, Israel (Ri.A., Ru.A.); and Department of Neurology, Barzilai Medical Center, Ashkelon, Israel, and Faculty of Health Sciences, Ben-Gurion University of the Negev, Be'er-Sheva, Israel (R.M.)
Multiple sclerosis (MS) is a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system (CNS), with a putative autoimmune origin and complex pathogenesis. Modification of the natural history of MS by reducing relapses and slowing disability accumulation was first attained in the 1990 s with the development of the first-generation disease-modifying therapies. Glatiramer acetate (GA), a copolymer of L-alanine, L-lysine, L-glutamic acid, and L-tyrosine, was discovered due to its ability to suppress the animal model of MS, experimental autoimmune encephalomyelitis.
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