Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.
axon regeneration
fibrotic scar
ischemia
neuroplasticity
stroke
Journal
Cell reports. Medicine
ISSN: 2666-3791
Titre abrégé: Cell Rep Med
Pays: United States
ID NLM: 101766894
Informations de publication
Date de publication:
22 12 2020
22 12 2020
Historique:
received:
10
06
2020
revised:
16
10
2020
accepted:
20
11
2020
entrez:
30
12
2020
pubmed:
31
12
2020
medline:
31
12
2020
Statut:
epublish
Résumé
Stroke leads to the degeneration of short-range and long-range axonal connections emanating from peri-infarct tissue, but it also induces novel axonal projections. However, this regeneration is hampered by growth-inhibitory properties of peri-infarct tissue and fibrotic scarring. Here, we tested the effects of epothilone B and epothilone D, FDA-approved microtubule-stabilizing drugs that are powerful modulators of axonal growth and scar formation, on neuroplasticity and motor outcomes in a photothrombotic mouse model of cortical stroke. We find that both drugs, when administered systemically 1 and 15 days after stroke, augment novel peri-infarct projections connecting the peri-infarct motor cortex with neighboring areas. Both drugs also increase the magnitude of long-range motor projections into the brainstem and reduce peri-infarct fibrotic scarring. Finally, epothilone treatment induces an improvement in skilled forelimb motor function. Thus, pharmacological microtubule stabilization represents a promising target for therapeutic intervention with a wide time window to ameliorate structural and functional sequelae after stroke.
Identifiants
pubmed: 33377130
doi: 10.1016/j.xcrm.2020.100159
pii: S2666-3791(20)30206-8
pmc: PMC7762779
doi:
Substances chimiques
Epothilones
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Pagination
100159Informations de copyright
© 2020 The Author(s).
Déclaration de conflit d'intérêts
H. Witte, A. Ertürk, F. Hellal, and F.B. filed a patent on the use of microtubule-stabilizing compounds for the treatment of lesions of CNS axons (European patent no. 1858498; European patent application EP 11 00 9155.0; US patent application 11/908,118).
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