%0 Journal Article
%A Kugler, Christof
%A Thielscher, Christian
%A Tambe, Bertrand A
%A Schwarz, Martin K
%A Halle, Annett
%A Bradke, Frank
%A Petzold, Gabor C
%T Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.
%J Cell reports / Medicine
%V 1
%N 9
%@ 2666-3791
%C Maryland Heights, MO
%I Elsevier
%M DZNE-2021-00295
%P 100159
%D 2020
%X 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.
%K Animals
%K Axons: drug effects
%K Central Nervous System: drug effects
%K Central Nervous System: physiopathology
%K Disease Models, Animal
%K Epothilones: pharmacology
%K Mammals
%K Motor Cortex: drug effects
%K Neuronal Plasticity: drug effects
%K Neurons: drug effects
%K Recovery of Function: drug effects
%K Recovery of Function: physiology
%K Stroke: drug therapy
%K axon regeneration (Other)
%K fibrotic scar (Other)
%K ischemia (Other)
%K neuroplasticity (Other)
%K stroke (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:33377130
%2 pmc:PMC7762779
%R 10.1016/j.xcrm.2020.100159
%U https://pub.dzne.de/record/154666