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Int. J. Mol. Sci. 2018, 19(7), 2019; https://doi.org/10.3390/ijms19072019

Effect of Inhibition of DNA Methylation Combined with Task-Specific Training on Chronic Stroke Recovery

1
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea
2
Department of Medical Science Konkuk University School of Medicine, Konkuk University, Seoul 05029, Korea
3
Department of Rehabilitation Medicine, Konkuk University School of Medicine, Konkuk University, Seoul 05029, Korea
*
Authors to whom correspondence should be addressed.
Received: 23 May 2018 / Revised: 7 July 2018 / Accepted: 9 July 2018 / Published: 11 July 2018
(This article belongs to the Special Issue Molecular Pharmacology and Pathology of Strokes)
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Abstract

To develop new rehabilitation therapies for chronic stroke, this study examined the effectiveness of task-specific training (TST) and TST combined with DNA methyltransferase inhibitor in chronic stroke recovery. Eight weeks after photothrombotic stroke, 5-Aza-2′-deoxycytidine (5-Aza-dC) infusion was done on the contralesional cortex for four weeks, with and without TST. Functional recovery was assessed using the staircase test, the cylinder test, and the modified neurological severity score (mNSS). Axonal plasticity and expression of brain-derived neurotrophic factor (BDNF) were determined in the contralateral motor cortex. TST and TST combined with 5-Aza-dC significantly improved the skilled reaching ability in the staircase test and ameliorated mNSS scores and cylinder test performance. TST and TST with 5-Aza-dC significantly increased the crossing fibers from the contralesional red nucleus, reticular formation in medullar oblongata, and dorsolateral spinal cord. Mature BDNF was significantly upregulated by TST and TST combined with 5-Azd-dC. Functional recovery after chronic stroke may involve axonal plasticity and increased mature BDNF by modulating DNA methylation in the contralesional cortex. Our results suggest that combined therapy to enhance axonal plasticity based on TST and 5-Aza-dC constitutes a promising approach for promoting the recovery of function in the chronic stage of stroke. View Full-Text
Keywords: stroke; chronic stage; task-specific training; DNA methylation; axonal plasticity; functional recovery; mature brain-derived neurotrophic factor stroke; chronic stage; task-specific training; DNA methylation; axonal plasticity; functional recovery; mature brain-derived neurotrophic factor
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This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).
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Choi, I.-A.; Lee, C.S.; Kim, H.Y.; Choi, D.-H.; Lee, J. Effect of Inhibition of DNA Methylation Combined with Task-Specific Training on Chronic Stroke Recovery. Int. J. Mol. Sci. 2018, 19, 2019.

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