CB1 receptor antagonism prevents long-term hyperexcitability after head injury by regulation of dynorphin-KOR system and mGluR5 in rat hippocampus.
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-κ 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.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Tiantan xili 6, Dongcheng, Beijing 100050, China.
Xiu
X
Wang
Beijing Jingmei Group General Hospital, Heishan Street 18, Mentougou, Beijing 102300, China.
Yao
Y
Wang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Tiantan xili 6, Dongcheng, Beijing 100050, China.
Chao
C
Zhang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Tiantan xili 6, Dongcheng, Beijing 100050, China.
Chang
C
Liu
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Tiantan xili 6, Dongcheng, Beijing 100050, China.
Baotian
B
Zhao
Department of Neurosurgery, The Second Hospital of Lanzhou University, Chengguan District, Lanzhou, Gansu 730030, China.
Naili
N
Wei
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Neurosurgical Institute, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Tiantan xili 6, Dongcheng, Beijing 100050, China.
Jian-Guo
JG
Zhang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Neurosurgical Institute, Tiantan xili 6, Dongcheng, Beijing 100050, China; Beijing Key Laboratory of Neurostimulation, Tiantan xili 6, Dongcheng, Beijing 100050, China. Electronic address: zhangkai62035@163.com.
Kai
K
Zhang
D000818:Animals; D001930:Brain Injuries / Q000150:complications*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D010433:Pentylenetetrazole; D010880:Piperidines / Q000008:administration & dosage; D011720:Pyrazoles / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D043884:Receptor, Cannabinoid, CB1 / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D064529:Receptor, Metabotropic Glutamate 5 / Q000378:metabolism*; D018094:Receptors, Metabotropic Glutamate / Q000378:metabolism; D017473:Receptors, Opioid, kappa / Q000378:metabolism*; D000077285:Rimonabant; D012640:Seizures / Q000139:chemically induced / Q000150:complications / Q000378:metabolism* / Q000517:prevention & control
C578937:Grm5 protein, rat; D010880:Piperidines; D011720:Pyrazoles; D043884:Receptor, Cannabinoid, CB1; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D017473:Receptors, Opioid, kappa; C104077:metabotropic glutamate receptor type 1; D000077285:Rimonabant; D010433:Pentylenetetrazole
Dynorphin; Endocannabinoid; Metabotropic glutamate receptor; Post-traumatic epilepsy; Prevention