Abnormal cannabidiol (abn-CBD) exerts neuroprotective effects in vivo and in vitro. In the present study, we investigated the impact of abn-CBD on the glial production of proinflammatory mediators and scar formation within in vitro models. Primary astrocytic-microglial cocultures and astrocytic cultures from neonatal C57BL/6 mice and CB2 receptor knockout mice were stimulated with lipopolysaccharide (LPS), and the concentrations of tumor necrosis factor α (TNFα), interleukin-6 (IL-6) and nitrite were determined. Furthermore, we performed a live cell microscopy-based scratch-wound assay. After LPS stimulation, TNFα, IL-6 and nitrite production was more strongly increased in cocultures than in isolated astrocytes. Abn-CBD treatment attenuated the LPS-induced production of TNFα and nitrite in cocultures, while IL-6 production remained unaltered. In isolated astrocytes, only LPS-induced TNFα production was reduced by abn-CBD. Similar effects were observed after abn-CBD application in cocultures of CB2 knockout mice. Interestingly, LPS-induced TNFα and nitrite levels were far lower in CB2 knockout cultures compared to wildtypes, while IL-6 levels did not differ. In the scratch-wound assay, treatment with abn-CBD decelerated wound closure when microglial cells were present. Our data shows a differential role of abn-CBD for modulation of glial inflammation and astrocytic scar formation. These findings provide new explanations for mechanisms behind the neuroprotective potential of abn-CBD.

中文翻译：

---

异常大麻二酚影响原代星形胶质细胞-小胶质细胞共培养物中促炎介质的产生和星形胶质细胞伤口闭合

异常大麻二酚（abn-CBD）在体内和体外发挥神经保护作用。在本研究中，我们在体外模型中研究了 abn-CBD 对促炎介质神经胶质产生和疤痕形成的影响。用脂多糖（LPS）刺激原代星形细胞-小胶质细胞共培养物以及新生C57BL/6小鼠和CB2受体敲除小鼠的星形细胞培养物，并测量肿瘤坏死因子α（TNFα）、白细胞介素6（IL-6）和亚硝酸盐的浓度。决定。此外，我们进行了基于活细胞显微镜的划痕实验。LPS 刺激后，共培养物中 TNFα、IL-6 和亚硝酸盐的产生比分离的星形胶质细胞更强烈地增加。Abn-CBD 处理减弱了共培养物中 LPS 诱导的 TNFα 和亚硝酸盐的产生，而 IL-6 的产生保持不变。在分离的星形胶质细胞中，abn-CBD 仅减少 LPS 诱导的 TNFα 产生。在 CB2 敲除小鼠的共培养中应用 abn-CBD 后，观察到类似的效果。有趣的是，与野生型相比，CB2 敲除培养物中 LPS 诱导的 TNFα 和亚硝酸盐水平远低于野生型，而 IL-6 水平没有差异。在划痕伤口试验中，当存在小胶质细胞时，使用 abn-CBD 治疗可减缓伤口闭合。我们的数据显示 abn-CBD 在调节神经胶质炎症和星形细胞疤痕形成方面的不同作用。这些发现为 abn-CBD 神经保护潜力背后的机制提供了新的解释。