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  • Title: Melatonin attenuates white matter damage after focal brain ischemia in rats by regulating the TLR4/NF-κB pathway.
    Author: Zhao Y, Wang H, Chen W, Chen L, Liu D, Wang X, Wang X.
    Journal: Brain Res Bull; 2019 Aug; 150():168-178. PubMed ID: 31158461.
    Abstract:
    OBJECTIVE: To assess the possible neuroprotective effects of melatonin against brain white matter damage via the Toll-like receptor 4 (TLR4)/ nuclear factor-kappa B (NF-κB) signaling pathway in focal cerebral ischemic rats. METHODS: Fifty-four Sprague-Dawley rats were randomly divided into the Sham, middle cerebral artery occlusion (MCAO), and melatonin groups. The successful MCAO models were evaluated by Laser Doppler flowmetry, magnetic resonance imaging (MRI) with T2-weighted imaging (T2WI) examination and 2, 3, 5-triphenyltetrazolium chloride (TTC) staining. White matter damage was assessed by myelin basic protein (MBP) immunohistochemical, Luxol Fast Blue (LFB) staining, and diffusion tensor imaging (DTI) examination. The proliferation of oligodendrocyte progenitor cells (OPCs) was examined by proliferating cell nuclear antigen (PCNA)/neural glial antigen 2 (NG2)/DAPI immunofluorescent staining. And the effects of melatonin therapy on the TLR4, NF-κB, and interleukin (IL)-1β proteins were examined by immunohistochemical staining. The correlation between the proliferating OPCs and TLR4 protein, IL-1β and TLR4 protein was respectively analyzed by linear regression analysis. RESULTS: The infarct volume was significantly reduced and white matter damage was also significantly alleviated in the melatonin group as compared with the MCAO group (P <  0.05), and there were more TLR4+, NF-κB+ and IL-1β+ cells in the MCAO group compared with the melatonin group (P <  0.01). Similarly, more PCNA+NG2+ cells were observed in the subventricular zone and white matter areas in the melatonin group compared with the MCAO group (P <  0.01). The number of TLR4+ cells was closely positively correlated with that of IL-1β+ cells, and negatively correlated with that of PCNA+NG2+ cells. CONCLUSIONS: In summary, melatonin could promote the proliferation of endogenous OPCs and suppress the expression of IL-1β protein via inhibiting TLR4/NF-κB signaling, thus alleviate the white matter damage in focal cerebral ischemic rats.
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