Nicotinamide Administration Improves Remyelination after Stroke

Aims. Stroke is a leading cause of morbidity and mortality. This study aimed to determine whether nicotinamide administration could improve remyelination after stroke and reveal the underlying mechanism. Methods. Adult male C57BL/6J mice were intraperitoneally (i.p.) administered with nicotinamide (...

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Main Authors: Congxiao Wang, Yi Zhang, Jie Ding, Zhen Zhao, Cheng Qian, Ying Luan, Gao-Jun Teng
Format: Article
Language:English
Published: Wiley 2017-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2017/7019803
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author Congxiao Wang
Yi Zhang
Jie Ding
Zhen Zhao
Cheng Qian
Ying Luan
Gao-Jun Teng
author_facet Congxiao Wang
Yi Zhang
Jie Ding
Zhen Zhao
Cheng Qian
Ying Luan
Gao-Jun Teng
author_sort Congxiao Wang
collection DOAJ
description Aims. Stroke is a leading cause of morbidity and mortality. This study aimed to determine whether nicotinamide administration could improve remyelination after stroke and reveal the underlying mechanism. Methods. Adult male C57BL/6J mice were intraperitoneally (i.p.) administered with nicotinamide (200 mg/kg, daily) or saline after stroke induced by photothrombotic occlusion of the middle cerebral artery. FK866 (3 mg/kg, daily, bis in die), an inhibitor of NAMPT, and ANA-12 (0.5 mg/kg, daily), an antagonist of tropomyosin-related kinase B (TrkB), were administered intraperitoneally 1 h before nicotinamide administration. Functional recovery, MRI, and histological assessment were performed after stroke at different time points. Results. The nicotinamide-treated mice showed significantly lower infarct area 7 d after stroke induction and significantly higher fractional anisotropy (FA) in the ipsilesional internal capsule (IC) 14 d after stroke induction than the other groups. Higher levels of NAD+, BDNF, and remyelination markers were observed in the nicotinamide-treated group. FK866 administration reduced NAD+ and BDNF levels in the nicotinamide-treated group. ANA-12 administration impaired the recovery from stroke with no effect on NAD+ and BDNF levels. Furthermore, lesser functional deficits were observed in the nicotinamide-treated group than in the control group. Conclusions. Nicotinamide administration improves remyelination after stroke via the NAD+/BDNF/TrkB pathway.
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spelling doaj-art-75308c84231b4c94bbbc2f51821d3ba12025-08-20T02:07:13ZengWileyNeural Plasticity2090-59041687-54432017-01-01201710.1155/2017/70198037019803Nicotinamide Administration Improves Remyelination after StrokeCongxiao Wang0Yi Zhang1Jie Ding2Zhen Zhao3Cheng Qian4Ying Luan5Gao-Jun Teng6Jiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaJiangsu Key Laboratory of Molecular and Functional Imaging, Department of Radiology, Zhongda Hospital, Medical School of Southeast University, Nanjing 210009, ChinaAims. Stroke is a leading cause of morbidity and mortality. This study aimed to determine whether nicotinamide administration could improve remyelination after stroke and reveal the underlying mechanism. Methods. Adult male C57BL/6J mice were intraperitoneally (i.p.) administered with nicotinamide (200 mg/kg, daily) or saline after stroke induced by photothrombotic occlusion of the middle cerebral artery. FK866 (3 mg/kg, daily, bis in die), an inhibitor of NAMPT, and ANA-12 (0.5 mg/kg, daily), an antagonist of tropomyosin-related kinase B (TrkB), were administered intraperitoneally 1 h before nicotinamide administration. Functional recovery, MRI, and histological assessment were performed after stroke at different time points. Results. The nicotinamide-treated mice showed significantly lower infarct area 7 d after stroke induction and significantly higher fractional anisotropy (FA) in the ipsilesional internal capsule (IC) 14 d after stroke induction than the other groups. Higher levels of NAD+, BDNF, and remyelination markers were observed in the nicotinamide-treated group. FK866 administration reduced NAD+ and BDNF levels in the nicotinamide-treated group. ANA-12 administration impaired the recovery from stroke with no effect on NAD+ and BDNF levels. Furthermore, lesser functional deficits were observed in the nicotinamide-treated group than in the control group. Conclusions. Nicotinamide administration improves remyelination after stroke via the NAD+/BDNF/TrkB pathway.http://dx.doi.org/10.1155/2017/7019803
spellingShingle Congxiao Wang
Yi Zhang
Jie Ding
Zhen Zhao
Cheng Qian
Ying Luan
Gao-Jun Teng
Nicotinamide Administration Improves Remyelination after Stroke
Neural Plasticity
title Nicotinamide Administration Improves Remyelination after Stroke
title_full Nicotinamide Administration Improves Remyelination after Stroke
title_fullStr Nicotinamide Administration Improves Remyelination after Stroke
title_full_unstemmed Nicotinamide Administration Improves Remyelination after Stroke
title_short Nicotinamide Administration Improves Remyelination after Stroke
title_sort nicotinamide administration improves remyelination after stroke
url http://dx.doi.org/10.1155/2017/7019803
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AT yizhang nicotinamideadministrationimprovesremyelinationafterstroke
AT jieding nicotinamideadministrationimprovesremyelinationafterstroke
AT zhenzhao nicotinamideadministrationimprovesremyelinationafterstroke
AT chengqian nicotinamideadministrationimprovesremyelinationafterstroke
AT yingluan nicotinamideadministrationimprovesremyelinationafterstroke
AT gaojunteng nicotinamideadministrationimprovesremyelinationafterstroke