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