Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.

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.

• Authors: Christof Kugler, Christian Thielscher, Bertrand A Tambe, Martin K Schwarz, Annett Halle, Frank Bradke, Gabor C Petzold
• Journal: Cell reports. Medicine (Cell Rep Med) Vol. 1 Issue 9 Pg. 100159 (12 22 2020) ISSN: 2666-3791 [Electronic] United States
• PMID: 33377130 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2020 The Author(s).

Chemical References

• Epothilones

Topics

• Animals
• Axons (drug effects)
• Central Nervous System (drug effects, physiopathology)
• Disease Models, Animal
• Epothilones (pharmacology)
• Mammals
• Motor Cortex (drug effects)
• Neuronal Plasticity (drug effects)
• Neurons (drug effects)
• Recovery of Function (drug effects, physiology)
• Stroke (drug therapy)