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000154666 1001_ $$0P:(DE-2719)2811853$$aKugler, Christof$$b0$$eFirst author
000154666 245__ $$aEpothilones Improve Axonal Growth and Motor Outcomes after Stroke in the Adult Mammalian CNS.
000154666 260__ $$aMaryland Heights, MO$$bElsevier$$c2020
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000154666 520__ $$aStroke leads to the degeneration of short-range and long-range axonal connections emanating from peri-infarct tissue, but it also induces novel axonal projections. However, this regeneration is hampered by growth-inhibitory properties of peri-infarct tissue and fibrotic scarring. Here, we tested the effects of epothilone B and epothilone D, FDA-approved microtubule-stabilizing drugs that are powerful modulators of axonal growth and scar formation, on neuroplasticity and motor outcomes in a photothrombotic mouse model of cortical stroke. We find that both drugs, when administered systemically 1 and 15 days after stroke, augment novel peri-infarct projections connecting the peri-infarct motor cortex with neighboring areas. Both drugs also increase the magnitude of long-range motor projections into the brainstem and reduce peri-infarct fibrotic scarring. Finally, epothilone treatment induces an improvement in skilled forelimb motor function. Thus, pharmacological microtubule stabilization represents a promising target for therapeutic intervention with a wide time window to ameliorate structural and functional sequelae after stroke.
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000154666 650_7 $$2Other$$aaxon regeneration
000154666 650_7 $$2Other$$afibrotic scar
000154666 650_7 $$2Other$$aischemia
000154666 650_7 $$2Other$$aneuroplasticity
000154666 650_7 $$2Other$$astroke
000154666 650_2 $$2MeSH$$aAnimals
000154666 650_2 $$2MeSH$$aAxons: drug effects
000154666 650_2 $$2MeSH$$aCentral Nervous System: drug effects
000154666 650_2 $$2MeSH$$aCentral Nervous System: physiopathology
000154666 650_2 $$2MeSH$$aDisease Models, Animal
000154666 650_2 $$2MeSH$$aEpothilones: pharmacology
000154666 650_2 $$2MeSH$$aMammals
000154666 650_2 $$2MeSH$$aMotor Cortex: drug effects
000154666 650_2 $$2MeSH$$aNeuronal Plasticity: drug effects
000154666 650_2 $$2MeSH$$aNeurons: drug effects
000154666 650_2 $$2MeSH$$aRecovery of Function: drug effects
000154666 650_2 $$2MeSH$$aRecovery of Function: physiology
000154666 650_2 $$2MeSH$$aStroke: drug therapy
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000154666 7001_ $$0P:(DE-HGF)0$$aThielscher, Christian$$b1
000154666 7001_ $$0P:(DE-2719)2812512$$aTambe, Bertrand A$$b2
000154666 7001_ $$0P:(DE-HGF)0$$aSchwarz, Martin K$$b3
000154666 7001_ $$0P:(DE-2719)2812038$$aHalle, Annett$$b4
000154666 7001_ $$0P:(DE-2719)2810270$$aBradke, Frank$$b5
000154666 7001_ $$0P:(DE-2719)2810273$$aPetzold, Gabor C$$b6$$eLast author
000154666 773__ $$0PERI:(DE-600)3019420-9$$a10.1016/j.xcrm.2020.100159$$gVol. 1, no. 9, p. 100159 -$$n9$$p100159$$tCell reports / Medicine$$v1$$x2666-3791$$y2020
000154666 8564_ $$uhttps://www.sciencedirect.com/science/article/pii/S2666379120302068
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