Dataset Information

Nicotinamide Administration Improves Remyelination after Stroke.

ABSTRACT:

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.

SUBMITTER: Wang C

PROVIDER: S-EPMC5471593 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

Nicotinamide Administration Improves Remyelination after Stroke.

Wang Congxiao C Zhang Yi Y Ding Jie J Zhao Zhen Z Qian Cheng C Luan Ying Y Teng Gao-Jun GJ

Neural plasticity 20170601

<h4>Aims</h4>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.<h4>Methods</h4>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, <i>bis in die</i>), an inhibitor of NAMPT, and ANA-12 ( ...[more]

PMID: 28656112

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Project description:BackgroundStroke is one of the most common neurological diseases in the world and is clinically manifested by transient or permanent brain dysfunction. It has a high mortality and disability rate, which severely affects people's health and diminishes the quality of life. However, there is no efficient treatment that can be considered curative and there are other less well-known theories of pathogenesis. Therefore, it is imperative to gain a full understanding of the pathophysiology of ischemia and to seek new therapeutic strategies.MethodsWe first examined Kir4.1 channel and myelin based protein (MBP) expression in brain tissues from acute ischemic patients by Western blotting. We then established a transient ischemic mouse model (tMCAO) to conduct molecular, cell biological, transmission electron microscopy and pharmacokinetic studies, as well as in Kir4.1 cKO mice. Finally, neuroimaging and behavioral analyses were used to examine whether activation of Kir4.1 channel by luteolin could contribute to neuronal functional recovery in ischemic stroke.FindingsIn acute ischemic stroke patients, we first demonstrated that Kir4.1 ion channels were greatly impaired and a severe demyelination of axons occurred in ischemic infarction area of cerebral cortex in these patients. Further evidence showed that the deficits of Kir4.1 channels in NG2 glia led to the myelin loss of axons in a transient ischemic mouse model (tMCAO). Treating ischemic mice with a natural botanical extract, luteolin augmented Kir4.1 channel currents in NG2 glia and consequently promoted remyelination of axons, alleviated the infarction area and ultimately improved motor function in a series of behavioral tests.InterpretationTargeting Kir4.1 ion channels expressed in NG2 glial cells by luteolin treatment highlights an effective therapeutic strategy for a prompt brain functional recovery in ischemic stroke.FundingThis work was supported by grants from the Ministry of Science and Technology China Brain Initiative (2022ZD0204702, to X.T.), the National Natural Science Foundation of China (82271466, 82171279, 31970904 and 31571063), the Program for Professor of Special Appointment (Eastern Scholar for Dr. X.T.) at Shanghai Institutions for Higher Learning (1510000084), Shanghai Pujiang Talent Award (15PJ1404600), Shanghai Municipal Science and Technology Major Project (2018SHZDZX05) and Shanghai Science and Technology Project (17411954000).

Dataset Information

Nicotinamide Administration Improves Remyelination after Stroke.

Aims

Methods

Results

Conclusions

Publications

Nicotinamide Administration Improves Remyelination after Stroke.

Similar Datasets

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