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The AMPAR Antagonist Perampanel Attenuates Traumatic Brain Injury Through Anti-Oxidative and Anti-Inflammatory Activity

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Abstract

Perampanel is a novel α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor (AMPAR) antagonist, approved in over 35 countries as an adjunctive therapy for the treatment of seizures. Recently, it was found to exert protective effects against ischemic neuronal injury in vitro. In the present study, we investigated the potential protective effects of perampanel in a traumatic brain injury (TBI) model in rats. Oral administration with perampanel at a dose of 5 mg/kg exerted no major organ-related toxicities. We found that perampanel significantly attenuated TBI-induced brain edema, brain contusion volume, and gross motor dysfunction. The results of Morris water maze test demonstrated that perampanel treatment also improved cognitive function after TBI. These neuroprotective effects were accompanied by reduced neuronal apoptosis, as evidenced by decreased TUNEL-positive cells in brain sections. Moreover, perampanel markedly inhibited lipid peroxidation and obviously preserved the endogenous antioxidant system after TBI. In addition, enzyme-linked immunosorbent assay (ELISA) was performed at 4 and 24 h after TBI to evaluate the expression of inflammatory cytokines. The results showed that perampanel suppressed the expression of pro-inflammatory cytokines TNF-α and IL-1β, whereas increased the levels of anti-inflammatory cytokines IL-10 and TGF-β1. These data show that the orally active AMPAR antagonist perampanel affords protection against TBI-induced neuronal damage and neurological dysfunction through anti-oxidative and anti-inflammatory activity.

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Acknowledgments

This work was supported by the National Natural Science Foundation of China (Nos. 81371447 and 81301037).

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    Authors and Affiliations

    1. Department of Neurosurgery, The 123th Hospital of PLA, Bengbu, 233010, Anhui, China

      Tao Chen & Yi-Long Qi

    2. Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, 100050, China

      Song-Bai Gui

    3. Department of Neurosurgery, Xijing Institute of Clinical Neuroscience, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, Shaanxi, China

      Tao Chen, Shu-Hui Dai, Peng Luo, Xiao-Fan Jiang & Zhou Fei

    4. Department of Neurosurgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, 233004, Anhui, China

      Zhi-Quan Jiang

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    1. Tao Chen
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    Tao Chen, Shu-Hui Dai and Zhi-Quan Jiang have contributed equally to this work.

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    Chen, T., Dai, SH., Jiang, ZQ. et al. The AMPAR Antagonist Perampanel Attenuates Traumatic Brain Injury Through Anti-Oxidative and Anti-Inflammatory Activity. Cell Mol Neurobiol 37, 43–52 (2017). https://doi.org/10.1007/s10571-016-0341-8

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