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CB1 receptor antagonism prevents long-term hyperexcitability after head injury by regulation of dynorphin-KOR system and mGluR5 in rat hippocampus

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机构: [1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Tiantan Xili 6, Beijing 100050, Peoples R China; [2]Beijing Jingmei Grp, Gen Hosp, Heishan St 18, Beijing 102300, Peoples R China; [3]Beijing Neurosurg Inst, Tiantan Xili 6, Beijing 100050, Peoples R China; [4]Beijing Key Lab Neurostimulat, Tiantan Xili 6, Beijing 100050, Peoples R China; [5]Lanzhou Univ, Hosp 2, Dept Neurosurg, Lanzhou 730030, Gansu, Peoples R China; [6]Beijing Tiantan Hosp, Dept Neurosurg, Tiantan Xili 6, Beijing 100050, Peoples R China
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关键词: Post-traumatic epilepsy Prevention Endocannabinoid Dynorphin Metabotropic glutamate receptor

摘要:
Both endocannabinoids and dynorphin are feedback messengers in nervous system that act at the presynaptic nerve terminal to inhibit transmitter release. Many studies showed the cannabinoid-opioid cross-modulation in antinociception, hypothermia, sedation and reward. The aim of this study was to assess the influence of early application of cannabinoid type 1 (CB1) receptor antagonism SR141716A after brain injury on dynorphin-x opioid receptor (KOR) system and the expression of metabotropic glutamate receptors (mGluRs) in a rat model of fluid percussion injury (FPI). Firstly, seizure latency induced by pentylenetetrazole was significantly prolonged 6 weeks after brain injury in group of SR141716A treatment. Then, PCR and western blot showed that SR141716A inhibited the long-term up regulation of CB1 receptors in hippocampus. However, SR141716A resulted in long-term potentiation of dynorphin release and did not influence the up-regulation of KOR in hippocampus after brain injury. Furthermore, SR141716A reverse the overexpression of mGluR5 in the late stage of brain injury. We propose that during the induction of epileptogenesis after brain injury, early application of CB1 receptor antagonism could prevent long-term hyperexcitability by up-regulation of dynorphin-KOR system and prevention of mGluR5 induced epileptogenesis in hippocampus. (C) 2016 Elsevier B.V. All rights reserved.

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出版当年[2015]版:
大类 | 3 区 医学
小类 | 4 区 神经科学
最新[2023]版:
大类 | 4 区 医学
小类 | 4 区 神经科学
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出版当年[2014]版:
Q2 NEUROSCIENCES
最新[2023]版:
Q3 NEUROSCIENCES

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第一作者机构: [1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Tiantan Xili 6, Beijing 100050, Peoples R China;
通讯作者:
通讯机构: [1]Capital Med Univ, Beijing Tiantan Hosp, Dept Neurosurg, Tiantan Xili 6, Beijing 100050, Peoples R China; [3]Beijing Neurosurg Inst, Tiantan Xili 6, Beijing 100050, Peoples R China; [4]Beijing Key Lab Neurostimulat, Tiantan Xili 6, Beijing 100050, Peoples R China; [6]Beijing Tiantan Hosp, Dept Neurosurg, Tiantan Xili 6, Beijing 100050, Peoples R China
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