PMID- 29997355
OWN - NLM
STAT- MEDLINE
DCOM- 20181102
LR  - 20181202
IS  - 1422-0067 (Electronic)
IS  - 1422-0067 (Linking)
VI  - 19
IP  - 7
DP  - 2018 Jul 11
TI  - Effect of Inhibition of DNA Methylation Combined with Task-Specific Training on 
      Chronic Stroke Recovery.
LID - 10.3390/ijms19072019 [doi]
LID - 2019
AB  - 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.
FAU - Choi, In-Ae
AU  - Choi IA
AD  - Center for Neuroscience Research, Institute of Biomedical Science and Technology, 
      Konkuk University, Seoul 05029, Korea. adia86@naver.com.
FAU - Lee, Cheol Soon
AU  - Lee CS
AD  - Center for Neuroscience Research, Institute of Biomedical Science and Technology, 
      Konkuk University, Seoul 05029, Korea. slaoa1428@naver.com.
FAU - Kim, Hahn Young
AU  - Kim HY
AD  - Center for Neuroscience Research, Institute of Biomedical Science and Technology, 
      Konkuk University, Seoul 05029, Korea. hykimmd@gmail.com.
FAU - Choi, Dong-Hee
AU  - Choi DH
AD  - Center for Neuroscience Research, Institute of Biomedical Science and Technology, 
      Konkuk University, Seoul 05029, Korea. dchoi@kku.ac.kr.
AD  - Department of Medical Science Konkuk University School of Medicine, Konkuk 
      University, Seoul 05029, Korea. dchoi@kku.ac.kr.
FAU - Lee, Jongmin
AU  - Lee J
AD  - Center for Neuroscience Research, Institute of Biomedical Science and Technology, 
      Konkuk University, Seoul 05029, Korea. leej@kuh.ac.kr.
AD  - Department of Rehabilitation Medicine, Konkuk University School of Medicine, 
      Konkuk University, Seoul 05029, Korea. leej@kuh.ac.kr.
LA  - eng
PT  - Journal Article
DEP - 20180711
PL  - Switzerland
TA  - Int J Mol Sci
JT  - International journal of molecular sciences
JID - 101092791
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 776B62CQ27 (Decitabine)
RN  - M801H13NRU (Azacitidine)
SB  - IM
MH  - Animals
MH  - Axons/metabolism
MH  - Azacitidine/administration & dosage/*analogs & derivatives/pharmacology
MH  - Brain-Derived Neurotrophic Factor/metabolism
MH  - DNA Methylation/*drug effects
MH  - Decitabine
MH  - Disease Models, Animal
MH  - Exercise
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Male
MH  - Neuronal Plasticity
MH  - Rats
MH  - Stroke/genetics/metabolism/physiopathology/*therapy
MH  - Stroke Rehabilitation/*methods
MH  - Task Performance and Analysis
PMC - PMC6073594
OTO - NOTNLM
OT  - DNA methylation
OT  - axonal plasticity
OT  - chronic stage
OT  - functional recovery
OT  - mature brain-derived neurotrophic factor
OT  - stroke
OT  - task-specific training
COIS- The authors declare no conflict of interest.
EDAT- 2018/07/13 06:00
MHDA- 2018/11/06 06:00
PMCR- 2018/07/01
CRDT- 2018/07/13 06:00
PHST- 2018/05/23 00:00 [received]
PHST- 2018/07/07 00:00 [revised]
PHST- 2018/07/09 00:00 [accepted]
PHST- 2018/07/13 06:00 [entrez]
PHST- 2018/07/13 06:00 [pubmed]
PHST- 2018/11/06 06:00 [medline]
PHST- 2018/07/01 00:00 [pmc-release]
AID - ijms19072019 [pii]
AID - ijms-19-02019 [pii]
AID - 10.3390/ijms19072019 [doi]
PST - epublish
SO  - Int J Mol Sci. 2018 Jul 11;19(7):2019. doi: 10.3390/ijms19072019.