Low sulfated heparan sulfate mimetic differentially affects repair in immune-mediated and toxin-induced experimental models of demyelination.
Animals
Mice
Cuprizone
/ toxicity
Sulfates
/ adverse effects
Oligodendroglia
/ pathology
Encephalomyelitis, Autoimmune, Experimental
/ chemically induced
Corpus Callosum
/ pathology
Central Nervous System Diseases
/ pathology
Heparitin Sulfate
/ therapeutic use
Mice, Inbred C57BL
Disease Models, Animal
Myelin Sheath
/ pathology
CNS repair
EAE
cuprizone
heparan sulfate
multiple sclerosis
myelination
Journal
Glia
ISSN: 1098-1136
Titre abrégé: Glia
Pays: United States
ID NLM: 8806785
Informations de publication
Date de publication:
07 2023
07 2023
Historique:
revised:
07
03
2023
received:
03
11
2022
accepted:
10
03
2023
medline:
10
5
2023
pubmed:
23
3
2023
entrez:
22
3
2023
Statut:
ppublish
Résumé
There is an urgent need for therapies that target the multicellular pathology of central nervous system (CNS) disease. Modified, nonanticoagulant heparins mimic the heparan sulfate glycan family and are known regulators of multiple cellular processes. In vitro studies have demonstrated that low sulfated modified heparin mimetics (LS-mHeps) drive repair after CNS demyelination. Herein, we test LS-mHep7 (an in vitro lead compound) in experimental autoimmune encephalomyelitis (EAE) and cuprizone-induced demyelination. In EAE, LS-mHep7 treatment resulted in faster recovery and rapidly reduced inflammation which was accompanied by restoration of animal weight. LS-mHep7 treatment had no effect on remyelination or on OLIG2 positive oligodendrocyte numbers within the corpus callosum in the cuprizone model. Further in vitro investigation confirmed that LS-mHep7 likely mediates its pro-repair effect in the EAE model by sequestering inflammatory cytokines, such as CCL5 which are upregulated during immune-mediated inflammatory attacks. These data support the future clinical translation of this next generation modified heparin as a treatment for CNS diseases with active immune system involvement.
Substances chimiques
Cuprizone
5N16U7E0AO
Sulfates
0
Heparitin Sulfate
9050-30-0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1683-1698Subventions
Organisme : Medical Research Council
ID : MR/V00381X/1
Pays : United Kingdom
Informations de copyright
© 2023 The Authors. GLIA published by Wiley Periodicals LLC.
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