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Int J Mol Sci. 2018 Jul 11;19(7). pii: E2019. doi: 10.3390/ijms19072019.

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

Author information

1
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea. adia86@naver.com.
2
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea. slaoa1428@naver.com.
3
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea. hykimmd@gmail.com.
4
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea. dchoi@kku.ac.kr.
5
Department of Medical Science Konkuk University School of Medicine, Konkuk University, Seoul 05029, Korea. dchoi@kku.ac.kr.
6
Center for Neuroscience Research, Institute of Biomedical Science and Technology, Konkuk University, Seoul 05029, Korea. leej@kuh.ac.kr.
7
Department of Rehabilitation Medicine, Konkuk University School of Medicine, Konkuk University, Seoul 05029, Korea. leej@kuh.ac.kr.

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.

KEYWORDS:

DNA methylation; axonal plasticity; chronic stage; functional recovery; mature brain-derived neurotrophic factor; stroke; task-specific training

PMID:
29997355
PMCID:
PMC6073594
DOI:
10.3390/ijms19072019
[Indexed for MEDLINE]
Free PMC Article

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