González-García Coral, Torres Irene Moreno, García-Hernández Ruth, Campos-Ruíz Lucía, Esparragoza Luis Rodríguez, Coronado María José, Grande Aranzazu García, García-Merino Antonio, Sánchez López Antonio J
Neuroimmunology Unit, Puerta de Hierro Hospital Research Institute, Universidad Autónoma de Madrid, Joaquín Rodrigo, 2, 28222, Majadahonda, Madrid, Spain.
Neuroimmunology Unit, Puerta de Hierro Hospital Research Institute, Universidad Autónoma de Madrid, Joaquín Rodrigo, 2, 28222, Majadahonda, Madrid, Spain.
Exp Neurol. 2017 Dec;298(Pt A):57-67. doi: 10.1016/j.expneurol.2017.08.017. Epub 2017 Sep 1.
Cannabidiol (CBD) is one of the most important compounds in Cannabis sativa, lacks psychotropic effects, and possesses a high number of therapeutic properties including the amelioration of experimental autoimmune encephalomyelitis (EAE). The aim of this study was to analyse the relative efficacy of CBD in adoptively transferred EAE (at-EAE), a model that allows better delineation of the effector phase of EAE. Splenocytes and lymph nodes from mice with actively induced EAE were cultured in the presence of MOG and IL-12 and inoculated intraperitoneally in recipient female C57BL/6J mice. The effects of CBD were evaluated using clinical scores and magnetic resonance imaging (MRI). In the central nervous system, the extent of cell infiltration, axonal damage, demyelination, microglial activation and cannabinoid receptors expression was assessed by immunohistochemistry. Lymph cell viability, apoptosis, oxidative stress and IL-6 production were measured in vitro. Preventive intraperitoneal treatment with CBD ameliorated the clinical signs of at-EAE, and this improvement was accompanied by a reduction of the apparent diffusion coefficient in the subiculum area of the brain. Inflammatory infiltration, axonal damage, and demyelination were reduced, and cannabinoid receptor expression was modulated. Incubation with CBD decreased encephalitogenic cell viability, increasing early apoptosis and reactive oxygen species (ROS) and decreasing IL-6 production. The reduction in viability was not mediated by CB, CB or GPR55 receptors. CBD markedly improved the clinical signs of at-EAE and reduced infiltration, demyelination and axonal damage. The CBD-mediated decrease in the viability of encephalitogenic cells involves ROS generation, apoptosis and a decrease in IL-6 production and may contribute to the therapeutic effect of this compound.
大麻二酚（CBD）是大麻中最重要的化合物之一，无精神活性，具有多种治疗特性，包括改善实验性自身免疫性脑脊髓炎（EAE）。本研究旨在分析CBD在过继转移型EAE（at-EAE）中的相对疗效，该模型能更好地描绘EAE的效应期。将主动诱导EAE的小鼠的脾细胞和淋巴结在髓鞘少突胶质细胞糖蛋白（MOG）和白细胞介素-12（IL-12）存在的情况下进行培养，并腹腔注射给受体雌性C57BL/6J小鼠。使用临床评分和磁共振成像（MRI）评估CBD的效果。在中枢神经系统中，通过免疫组织化学评估细胞浸润、轴突损伤、脱髓鞘、小胶质细胞活化和大麻素受体表达的程度。体外测量淋巴细胞活力、凋亡、氧化应激和IL-6的产生。CBD腹腔预防性治疗改善了at-EAE的临床症状，同时脑下托区域的表观扩散系数降低。炎症浸润、轴突损伤和脱髓鞘减少，大麻素受体表达得到调节。与CBD孵育降低了致脑炎细胞的活力，增加了早期凋亡和活性氧（ROS），并减少了IL-6的产生。活力的降低不是由CB1、CB2或GPR55受体介导的。CBD显著改善了at-EAE的临床症状，减少了浸润、脱髓鞘和轴突损伤。CBD介导的致脑炎细胞活力降低涉及ROS生成、凋亡和IL-6产生减少，可能有助于该化合物的治疗效果。
