Cerebellar pathology in multiple sclerosis and experimental autoimmune encephalomyelitis: current status and future directions.
Cerebellum
deep cerebellar nuclei
experimental autoimmune encephalomyelitis
multiple sclerosis
neuroinflammation
Journal
Journal of central nervous system disease
ISSN: 1179-5735
Titre abrégé: J Cent Nerv Syst Dis
Pays: United States
ID NLM: 101595026
Informations de publication
Date de publication:
2023
2023
Historique:
received:
28
05
2023
accepted:
15
10
2023
medline:
9
11
2023
pubmed:
9
11
2023
entrez:
9
11
2023
Statut:
epublish
Résumé
Recent decades have witnessed significant progress in understanding mechanisms driving neurodegeneration and disease progression in multiple sclerosis (MS), but with a focus on the cerebrum. In contrast, there have been limited studies of cerebellar disease, despite the common occurrence of cerebellar symptoms in this disorder. These rare studies, however, highlight the early cerebellar involvement in disease development and an association between the early occurrence of cerebellar lesions and risk of worse prognosis. In parallel developments, it has become evident that far from being a region specialized in movement control, the cerebellum plays a crucial role in cognitive function, via circuitry connecting the cerebellum to association areas of the cerebrum. This complexity, coupled with challenges in imaging of the cerebellum have been major obstacles in the appreciation of the spatio-temporal evolution of cerebellar damage in MS and correlation with disability and progression. MS studies based on animal models have relied on an induced neuroinflammatory disease known as experimental autoimmune encephalomyelitis (EAE), in rodents and non-human primates (NHP). EAE has played a critical role in elucidating mechanisms underpinning tissue damage and been validated for the generation of proof-of-concept for cerebellar pathological processes relevant to MS. Additionally, rodent and NHP studies have formed the cornerstone of current knowledge of functional anatomy and cognitive processes. Here, we propose that improved insight into consequences of cerebellar damage in MS at the functional, cellular and molecular levels would be gained by more extensive characterization of EAE cerebellar pathology combined with the power of experimental paradigms in the field of cognition. Such combinatorial approaches would lead to improved potential for the development of MS sensitive markers and evaluation of candidate therapeutics.
Identifiants
pubmed: 37942276
doi: 10.1177/11795735231211508
pii: 10.1177_11795735231211508
pmc: PMC10629308
doi:
Types de publication
Journal Article
Review
Langues
eng
Pagination
11795735231211508Informations de copyright
© The Author(s) 2023.
Déclaration de conflit d'intérêts
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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