title: Cannabinoid receptor 2 activation restricts fibrosis and alleviates hydrocephalus after intraventricular hemorrhage.
abstract: Fibrosis in ventricular system has a role in hydrocephalus following intraventricular hemorrhage (IVH). The cannabinoid receptor 2 (CB2) has been reported to participate in alleviating the fibrosis process of many diseases. However, its role in fibrosis after IVH was unclear so far, and we hypothesized that CB2 activation has potential to attenuate hydrocephalus after IVH via restricting fibrosis. So the present study was designed to investigate this hypothesis in a modified rat IVH model. Autologous non-anticoagulative blood injection model was induced to mimic ventricular extension of hemorrhage in adult Sprague-Dawley rats. Rats were randomized to receive JWH-133(CB2 agonist), SR144528 (CB2 antagonist) or saline. The lateral ventricular volumes, fibrosis in the subarachnoid space and ventricular wall, transforming growth factor-β 1(TGF-β1) in cerebrospinal fluid and brain tissue, and animal neurological scores were measured to evaluate the effects of CB2 in hydrocephalus following IVH. CB2 agonist JWH-133 significantly decreased the lateral ventricular volumes, improved the associated neurological deficits, down-regulated TGF-β1 expression, and alleviated fibrosis in the subarachnoid space and ventricular wall after IVH. All of these effects were reversed by SR144528. In conclusion, CB2 may have anti-fibrogenic effects after IVH. CB2 agonist suppressed fibrosis of ventricular system and alleviated hydrocephalus following IVH, which is partly mediated by inhibiting TGF-β1.
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Qiang
authors: Q
authors: Tan
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Qianwei
authors: Q
authors: Chen
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Zhou
authors: Z
authors: Feng
authors: Department of Nutrition, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Xia
authors: X
authors: Shi
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Jun
authors: J
authors: Tang
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Yihao
authors: Y
authors: Tao
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Bing
authors: B
authors: Jiang
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Liang
authors: L
authors: Tan
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Hua
authors: H
authors: Feng
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Gang
authors: G
authors: Zhu
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China; Department of Neurosurgery, Sichuan Provincial Corps Hospital, Chinese People's Armed Police Forces, Leshan, People's Republic of China. Electronic address: yangyunfeng7199@sina.com.
authors: Yunfeng
authors: Y
authors: Yang
authors: Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: zhichen@tmmu.edu.cn.
authors: Zhi
authors: Z
authors: Chen
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology / Q000503:physiopathology; D001892:Camphanes / Q000494:pharmacology; D063386:Cannabinoid Receptor Agonists / Q000494:pharmacology; D063387:Cannabinoid Receptor Antagonists / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D002543:Cerebral Hemorrhage / Q000150:complications / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D005355:Fibrosis / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology; D006849:Hydrocephalus / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011720:Pyrazoles / Q000494:pharmacology; D011897:Random Allocation; D017207:Rats, Sprague-Dawley; D043885:Receptor, Cannabinoid, CB2 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
chemical_list: D001892:Camphanes; D063386:Cannabinoid Receptor Agonists; D063387:Cannabinoid Receptor Antagonists; D002186:Cannabinoids; C469526:Cnr2 protein, rat; D018696:Neuroprotective Agents; D011720:Pyrazoles; D043885:Receptor, Cannabinoid, CB2; C110630:SR 144528; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; C432747:1,1-dimethylbutyl-1-deoxy-Delta(9)-THC
keywords: Cannabinoid receptor 2; Fibrosis; Hydrocephalus; Intracerebral hemorrhage; Intraventricular hemorrhage; Transforming growth factor-β 1