Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 6, 50139 Florence, Italy.
Farmacia del Madonnone, Via Aretina 9R, 50135 Florence, Italy.
Int J Mol Sci. 2021 Sep 9;22(18):9773. doi: 10.3390/ijms22189773.
(1) Background: Over the past 10 years, a number of scientific studies have demonstrated the therapeutic potential of cannabinoid compounds present in the and plants. However, their role in mechanisms leading to neurodegeneration following cerebral ischemia is yet unclear. (2) Methods: We investigated the effects of extracts (Bedrocan, FM2) or selected cannabinoids (Δ-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabigerol) in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation (OGD), an in vitro model of forebrain global ischemia. Cell death in the CA1 subregion of slices was quantified by propidium iodide fluorescence, and morphological analysis and tissue organization were examined by immunohistochemistry and confocal microscopy. (3) Results: Incubation with the Bedrocan extract or THC exacerbated, whereas incubation with the FM2 extract or cannabidiol attenuated CA1 injury induced by OGD. Δ-THC toxicity was prevented by CB1 receptor antagonists, the neuroprotective effect of cannabidiol was blocked by TRPV2, 5-HT1A, and PPARγ antagonists. Confocal microscopy confirmed that CBD, but not THC, had a significant protective effect toward neuronal damage and tissue disorganization caused by OGD in organotypic hippocampal slices. (4) Conclusions: Our results suggest that cannabinoids play different roles in the mechanisms of post-ischemic neuronal death. In particular, appropriate concentrations of CBD or CBD/THC ratios may represent a valid therapeutic intervention in the treatment of post-ischemic neuronal death.
(1) 背景：在过去的 10 年中，许多科学研究已经证明了大麻素化合物在大麻和印度大麻植物中的治疗潜力。然而，它们在脑缺血后导致神经退行性变的机制中的作用尚不清楚。(2) 方法：我们研究了大麻素提取物（Bedrocan、FM2）或选定的大麻素（Δ-四氢大麻酚（THC）、大麻二酚（CBD）和大麻萜酚）在暴露于氧葡萄糖剥夺（OGD）的大鼠器官型海马切片中的作用，OGD 是一种体外前脑全脑缺血模型。通过碘化丙啶荧光定量切片 CA1 区的细胞死亡，通过免疫组织化学和共聚焦显微镜检查形态分析和组织组织。(3) 结果：Bedrocan 提取物或 THC 的孵育加剧了 OGD 诱导的 CA1 损伤，而 FM2 提取物或 CBD 的孵育则减轻了 CA1 损伤。CB1 受体拮抗剂可预防 Δ-THC 毒性，TRPV2、5-HT1A 和 PPARγ 拮抗剂可阻断 CBD 的神经保护作用。共聚焦显微镜证实，与 THC 相比，CBD 对 OGD 引起的器官型海马切片神经元损伤和组织紊乱具有显著的保护作用。(4) 结论：我们的结果表明，大麻素在缺血后神经元死亡的机制中发挥不同的作用。特别是，适当浓度的 CBD 或 CBD/THC 比值可能代表缺血后神经元死亡治疗的有效治疗干预。
