Journal Article

DZNE-2021-00295

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.

Kugler, C. (First author)DZNE* ; Thielscher, C. ; Tambe, B. A.DZNE* ; Schwarz, M. K. ; Halle, A.DZNE* ; Bradke, F.DZNE* ; Petzold, G. C. (Last author)DZNE*

2020
Elsevier Maryland Heights, MO

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Please use a persistent id in citations: doi:10.1016/j.xcrm.2020.100159

Abstract: 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.

Keyword(s): Animals (MeSH) ; Axons: drug effects (MeSH) ; Central Nervous System: drug effects (MeSH) ; Central Nervous System: physiopathology (MeSH) ; Disease Models, Animal (MeSH) ; Epothilones: pharmacology (MeSH) ; Mammals (MeSH) ; Motor Cortex: drug effects (MeSH) ; Neuronal Plasticity: drug effects (MeSH) ; Neurons: drug effects (MeSH) ; Recovery of Function: drug effects (MeSH) ; Recovery of Function: physiology (MeSH) ; Stroke: drug therapy (MeSH) ; axon regeneration ; fibrotic scar ; ischemia ; neuroplasticity ; stroke

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Contributing Institute(s):

1. Vascular Neurology (AG Petzold ; AG Petzold)
2. Microglia and Neuroinflammation (AG Halle)
3. Axon Growth and Regeneration (AG Bradke)

Research Program(s):

1. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Experiment(s):

1. Light Microscope Facility (CRFS-LMF) / Bonn
2. Image and Data Analysis Facility (CRFS-IDAF) / Bonn

Appears in the scientific report 2020

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; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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