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Int. J. Mol. Sci. 2014, 15(2), 2207-2222; doi:10.3390/ijms15022207
Article

Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury

1,2,†
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1,3,†
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2
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1,3
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1,3
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1,3
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3,4,5
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4, 2,*  and 1,3,4,5,*
1 Department of Rehabilitation Science, Graduate School of Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea 2 National Primate Research Center (NPRC), Korea Research Institute of Bioscience and Biotechnology (KRIBB), 30 Yeongudanji-ro, Ochang, Chung-buk 363-883, Korea 3 Cardiovascular & Metabolic Disease Center, College of Biomedical Science & Engineering, Inje University, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea 4 Department of Physical Therapy, College of Biomedical Science & Engineering, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea 5 Ubiquitous Healthcare Research Center, 197 Inje-ro, Gimhae, Gyeong-nam 621-749, Korea These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 18 November 2013 / Revised: 16 January 2014 / Accepted: 24 January 2014 / Published: 30 January 2014
(This article belongs to the Special Issue Neuroprotective Strategies 2014)
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Abstract

Endogenous neural stem/progenitor cells (eNSPCs) proliferate and differentiate into neurons and glial cells after spinal cord injury (SCI). We have previously shown that melatonin (MT) plus exercise (Ex) had a synergistic effect on functional recovery after SCI. Thus, we hypothesized that combined therapy including melatonin and exercise might exert a beneficial effect on eNSPCs after SCI. Melatonin was administered twice a day and exercise was performed on a treadmill for 15 min, six days per week for 3 weeks after SCI. Immunohistochemistry and RT-PCR analysis were used to determine cell population for late response, in conjunction with histological examination and motor function test. There was marked improvement in hindlimb function in SCI+MT+Ex group at day 14 and 21 after injury, as documented by the reduced size of the spinal lesion and a higher density of dendritic spines and axons; such functional improvements were associated with increased numbers of BrdU-positive cells. Furthermore, MAP2 was increased in the injured thoracic segment, while GFAP was increased in the cervical segment, along with elevated numbers of BrdU-positive nestin-expressing eNSPCs in the SCI+MT+Ex group. The dendritic spine density was augmented markedly in SCI+MT and SCI+MT+Ex groups.These results suggest a synergistic effect of SCI+MT+Ex might create a microenvironment to facilitate proliferation of eNSPCs to effectively replace injured cells and to improve regeneration in SCI.
Keywords: spinal cord injury; melatonin; functional recovery; endogenous neural stem/progenitor; therapeutic exercise spinal cord injury; melatonin; functional recovery; endogenous neural stem/progenitor; therapeutic exercise
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Lee, Y.; Lee, S.; Lee, S.-R.; Park, K.; Hong, Y.; Lee, M.; Park, S.; Jin, Y.; Chang, K.-T.; Hong, Y. Beneficial Effects of Melatonin Combined with Exercise on Endogenous Neural Stem/Progenitor Cells Proliferation after Spinal Cord Injury. Int. J. Mol. Sci. 2014, 15, 2207-2222.

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