國家衛生研究院 NHRI:Item 3990099045/13461
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    Please use this identifier to cite or link to this item: http://ir.nhri.org.tw/handle/3990099045/13461


    Title: Naltrexone is neuroprotective against traumatic brain injury in mu opioid receptor knockout mice
    Authors: Wang, YS;Hung, TW;Bae, EK;Wu, KJ;Hsieh, W;Yu, SJ
    Contributors: Center for Neuropsychiatric Research
    Abstract: AIMS: Naltrexone is a mu opioid receptor (MOR) antagonist used to treat drug dependence in patients. Previous reports indicated that MOR antagonists reduced neurodegeneration and inflammation after brain injury. The purpose of this study was to evaluate the neuroprotective effect of naltrexone in cell culture and a mouse model of traumatic brain injury (TBI). METHODS: The neuroprotective effect of naltrexone was examined in primary cortical neurons co-cultured with BV2 microglia. Controlled cortical impact (CCI) was delivered to the left cerebral cortex of adult male MOR wild-type (WT) and knockout (KO) mice. Naltrexone was given daily for 4 days, starting from day 2 after lesioning. Locomotor activity was evaluated on day 5 after the CCI. Brain tissues were collected for immunostaining, Western, and qPCR analysis. RESULTS: Glutamate reduced MAP2 immunoreactivity (-ir), while increased IBA1-ir in neuron/BV2 co-culture; both responses were antagonized by naltrexone. TBI significantly reduced locomotor activity and increased the expression of IBA1, iNOS, and CD4 in the lesioned cortex. Naltrexone significantly and equally antagonized the motor deficits and expression of IBA1 and iNOS in WT and KO mice. TBI-mediated CD4 protein production was attenuated by naltrexone in WT mice, but not in KO mice. CONCLUSION: Naltrexone reduced TBI-mediated neurodegeneration and inflammation in MOR WT and KO mice. The protective effect of naltrexone involves non-MOR and MOR mechanisms.
    Date: 2021-07
    Relation: CNS Neuroscience & Therapeutics. 2021 Jul;27(7):831-841.
    Link to: http://dx.doi.org/10.1111/cns.13655
    JIF/Ranking 2023: http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=NHRI&SrcApp=NHRI_IR&KeyISSN=1755-5930&DestApp=IC2JCR
    Cited Times(WOS): https://www.webofscience.com/wos/woscc/full-record/WOS:000652480100001
    Cited Times(Scopus): https://www.scopus.com/inward/record.url?partnerID=HzOxMe3b&scp=85106301345
    Appears in Collections:[Seong-Jin Yu] Periodical Articles

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