Journal
CNS NEUROSCIENCE & THERAPEUTICS
Volume 27, Issue 7, Pages 831-841Publisher
WILEY
DOI: 10.1111/cns.13655
Keywords
inflammation; mu opioid receptor; naltrexone; traumatic brain injury
Categories
Funding
- National Health Research Institutes, Taiwan [NP-106-PP-02, NP-107-PP-02]
- Ministry of Science and Technology, Taiwan [MOST 108-2320-B-400 -023]
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Naltrexone has shown neuroprotective effects in cell culture and a mouse model of traumatic brain injury by reducing neurodegeneration and inflammation. The drug also improved motor deficits and modulated the expression of specific proteins related to brain injury.
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.
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