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000140031 0247_ $$2doi$$a10.1016/j.expneurol.2017.12.001
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000140031 037__ $$aDZNE-2020-06353
000140031 041__ $$aEnglish
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000140031 1001_ $$0P:(DE-2719)2810285$$aRuschel, Jörg$$b0$$eFirst author$$udzne
000140031 245__ $$aSystemic administration of epothilone D improves functional recovery of walking after rat spinal cord contusion injury.
000140031 260__ $$aOrlando, Fla.$$bAcademic Press$$c2018
000140031 264_1 $$2Crossref$$3print$$bElsevier BV$$c2018-08-01
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000140031 520__ $$aCentral nervous system (CNS) injuries cause permanent impairments of sensorimotor functions as mature neurons fail to regenerate their severed axons. The poor intrinsic growth capacity of adult CNS neurons and the formation of an inhibitory lesion scar are key impediments to axon regeneration. Systemic administration of the microtubule stabilizing agent epothilone B promotes axon regeneration and recovery of motor function by activating the intrinsic axonal growth machinery and by reducing the inhibitory fibrotic lesion scar. Thus, epothilones hold clinical promise as potential therapeutics for spinal cord injury. Here we tested the efficacy of epothilone D, an epothilone B analog with a superior safety profile. By using liquid chromatography and mass spectrometry (LC/MS), we found adequate CNS penetration and distribution of epothilone D after systemic administration, confirming the suitability of the drug for non-invasive CNS treatment. Systemic administration of epothilone D reduced inhibitory fibrotic scarring, promoted regrowth of injured raphespinal fibers and improved walking function after mid-thoracic spinal cord contusion injury in adult rats. These results confirm that systemic administration of epothilones is a valuable therapeutic strategy for CNS regeneration and repair after injury and provides a further advance for potential clinical translation.
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000140031 7001_ $$0P:(DE-2719)2810270$$aBradke, Frank$$b1$$udzne
000140031 77318 $$2Crossref$$3journal-article$$a10.1016/j.expneurol.2017.12.001$$b : Elsevier BV, 2018-08-01$$p243-249$$tExperimental Neurology$$v306$$x0014-4886$$y2018
000140031 773__ $$0PERI:(DE-600)1466932-8$$a10.1016/j.expneurol.2017.12.001$$gVol. 306, p. 243 - 249$$p243-249$$q306<243 - 249$$tExperimental neurology$$v306$$x0014-4886$$y2018
000140031 8564_ $$uhttps://www.sciencedirect.com/science/article/abs/pii/S0014488617303308?via%3Dihub
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