國家衛生研究院 NHRI:Item 3990099045/15092
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/15092


    Title: Probucol treatment after traumatic brain injury activates BDNF/TrkB pathway, promotes neuroregeneration and ameliorates functional deficits in mice
    Authors: Chen, CM;Gung, PY;Ho, YC;Hamdin, CD;Yet, SF
    Contributors: Institute of Cellular and Systems Medicine;NHRI Graduate Student Program
    Abstract: BACKGROUND AND PURPOSE: Traumatic brain injury (TBI) is a major cause of mortality and morbidity worldwide, yet pharmacotherapies for TBI are currently lacking. Neuroregeneration is important in brain repair and functional recovery. In this study, probucol, a cholesterol-lowering drug with established safety profiles, was examined for its therapeutic effects and neuroregenerative actions in TBI. EXPERIMENTAL APPROACH: Male mice were subjected to the controlled cortical impact model of TBI, followed by daily administration of probucol. Neurological and cognitive functions were evaluated. Histological analyses of the neocortex and hippocampus were performed to detect the lesion, dendritic degeneration (microtubule-associated protein 2), synaptic density (synaptophysin), neurogenesis (doublecortin), brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) activation. Involvement of BDNF/TrkB pathway in probucol-mediated effects was examined in primary cultures of cortical neurons. KEY RESULTS: Probucol reduced brain lesion volume, enhanced the recovery of body symmetry, improved motor function and attenuated memory dysfunction after TBI. Meanwhile, probucol promoted post-injury dendritic growth and synaptogenesis and increased hippocampal proliferating neuronal progenitor cells, along with the formation as well as the survival of newborn neurons. Moreover, probucol enhances BDNF expression and TrkB activation. In vitro, probucol promoted neurite outgrowth, which was inhibited by a selective TrkB antagonist ANA-12. CONCLUSIONS AND IMPLICATIONS: Probucol enhanced functional restoration and ameliorated cognitive impairment after TBI by promoting post-injury neuronal remodelling and neurogenesis. Increased activation of BDNF/TrkB pathway by probucol, at least in part, contributed to the neuroregenerative effects of probucol. Together, it may be promising to repurpose probucol for TBI.
    Date: 2023-10
    Relation: British Journal of Pharmacology. 2023 Oct;180(20):2605-2622.
    Link to: http://dx.doi.org/10.1111/bph.16157
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=0007-1188&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:001016299800001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85162878621
    Appears in Collections:[Shaw-Fang Yet] Periodical Articles
    [Others] Periodical Articles

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