TY  - JOUR
AU  - Kugler, Christof
AU  - Thielscher, Christian
AU  - Tambe, Bertrand A
AU  - Schwarz, Martin K
AU  - Halle, Annett
AU  - Bradke, Frank
AU  - Petzold, Gabor C
TI  - Epothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.
JO  - Cell reports / Medicine
VL  - 1
IS  - 9
SN  - 2666-3791
CY  - Maryland Heights, MO
PB  - Elsevier
M1  - DZNE-2021-00295
SP  - 100159
PY  - 2020
AB  - 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.
KW  - Animals
KW  - Axons: drug effects
KW  - Central Nervous System: drug effects
KW  - Central Nervous System: physiopathology
KW  - Disease Models, Animal
KW  - Epothilones: pharmacology
KW  - Mammals
KW  - Motor Cortex: drug effects
KW  - Neuronal Plasticity: drug effects
KW  - Neurons: drug effects
KW  - Recovery of Function: drug effects
KW  - Recovery of Function: physiology
KW  - Stroke: drug therapy
KW  - axon regeneration (Other)
KW  - fibrotic scar (Other)
KW  - ischemia (Other)
KW  - neuroplasticity (Other)
KW  - stroke (Other)
LB  - PUB:(DE-HGF)16
C6  - pmid:33377130
C2  - pmc:PMC7762779
DO  - DOI:10.1016/j.xcrm.2020.100159
UR  - https://pub.dzne.de/record/154666
ER  -