Tan Qiang, Chen Qianwei, Feng Zhou, Shi Xia, Tang Jun, Tao Yihao, Jiang Bing, Tan Liang, Feng Hua, Zhu Gang, Yang Yunfeng, Chen Zhi
Department of Neurosurgery, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Department of Nutrition, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
Brain Res. 2017 Jan 1;1654(Pt A):24-33. doi: 10.1016/j.brainres.2016.10.016. Epub 2016 Oct 18.
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.
脑室系统纤维化在脑室内出血（IVH）后的脑积水形成中起作用。据报道，大麻素受体2（CB2）参与减轻多种疾病的纤维化过程。然而，其在IVH后纤维化中的作用迄今尚不清楚，我们推测CB2激活有可能通过限制纤维化来减轻IVH后的脑积水。因此，本研究旨在在改良的大鼠IVH模型中研究这一假设。采用自体非抗凝性血液注射模型模拟成年Sprague-Dawley大鼠的脑室出血扩展。将大鼠随机分为接受JWH-133（CB2激动剂）、SR144528（CB2拮抗剂）或生理盐水组。测量侧脑室体积、蛛网膜下腔和室壁的纤维化、脑脊液和脑组织中的转化生长因子-β1（TGF-β1）以及动物神经学评分，以评估CB2在IVH后脑积水中的作用。CB2激动剂JWH-133显著降低了侧脑室体积，改善了相关神经功能缺损，下调了TGF-β1表达，并减轻了IVH后蛛网膜下腔和室壁的纤维化。所有这些作用均被SR144528逆转。总之，CB2在IVH后可能具有抗纤维化作用。CB2激动剂抑制脑室系统纤维化并减轻IVH后脑积水，这部分是通过抑制TGF-β1介导的。
