Abstract：
Background: Status epilepticus (SE) is a series of seizures that can lead to serious neurological damages. Cannabidiol (CBD) is extracted from the cannabis plant, which has been approved as an antiseizure medication. This study aimed to determine the efficacy of various doses of CBD on lithium-pilocarpine-induced SE in rats and possible involvement of multiple pharmacological pathways. We hypothesized that cannabinoid receptors type 1 (CB1) and CB2, as well as GABAA receptors, might have important roles in the anticonvulsant effects of CBD against SE by its anti-inflammatory effects. Methods: SE was induced by intraperitoneal (i.p.) injection of lithium (127 mg/kg, i.p.) and pilocarpine (60 mg/kg, i.p., 20 h after lithium). Forty-two male rats were divided into seven groups (including control and sham groups), and the treated groups received different doses of CBD (1, 3, 5, 10, and 25 mg/kg, i.p.). SE score was recorded over the next 2 h following pilocarpine injection. Then, we measured the levels of pro-inflammatory cytokines, including interleukin (IL)-lβ and tumor necrosis factor (TNF)-α, using ELISA kits. Also we analyzed the expression of CB1, CB2, and GABAA receptors using the Western blot technique. Results: CBD at 5 mg/kg significantly reduced Racine\'s scale and duration of seizures, and increased the onset time of seizure. Moreover, CBD 5 mg/kg caused significant reductions in the elevated levels of IL-lβ and TNF-α, as well as a significant increase in the decreased level of CB1 receptor expression compared to the control group. In other word, CBD reverted the effects of SE in terms of neuroinflammation and CB1 receptor. Based on the obtained results, CBD was not able to restore the declined levels of CB2 or GABAA receptors. Conclusion: Our study found anticonvulsant effects of CBD on the SE rat model induced by lithium-pilocarpine with probable involvement of CB1 receptors and anti-inflammatory effects by reducing IL-1β and TNF-α markers independent of CB2 and GABAA receptors.
摘要：
背景：癫痫持续状态（SE）是一系列可导致严重神经系统损害的癫痫发作。大麻二酚（CBD）是从大麻植物中提取的，已被批准为抗癫痫药物。这项研究旨在确定各种剂量的CBD对大鼠中锂-毛果芸香碱诱导的SE的功效以及多种药理途径的可能参与。我们假设大麻素受体1型（CB1）和CB2，以及GABAA受体，通过其抗炎作用，可能在CBD对SE的抗惊厥作用中起重要作用。方法：通过腹膜内（i.p.）注射锂（127mg/kg，i.p.）和毛果芸香碱（60mg/kg，i.p.,锂后20小时)。将42只雄性大鼠分为7组(包括对照组和假手术组),治疗组接受不同剂量的CBD（1、3、5、10和25mg/kg，i.p.）。在接下来的2小时内记录毛果芸香碱注射后的SE评分。然后，我们测量了促炎细胞因子的水平，包括白细胞介素（IL）-1β和肿瘤坏死因子（TNF）-α，使用ELISA试剂盒。我们还使用Westernblot技术分析了CB1，CB2和GABAA受体的表达。结果：5mg/kg的CBD显着降低了Racine的发作规模和持续时间，并增加了癫痫发作的时间。此外，CBD5mg/kg导致IL-1β和TNF-α水平升高显着降低，以及与对照组相比，CB1受体表达水平的降低显着增加。换句话说,CBD逆转了SE在神经炎症和CB1受体方面的作用。根据获得的结果，CBD无法恢复CB2或GABAA受体水平的下降。结论：我们的研究发现CBD对锂-毛果芸香碱诱导的SE大鼠模型的抗惊厥作用，可能涉及CB1受体，并通过降低IL-1β和TNF-α标志物而独立于CB2和GABAA受体而具有抗炎作用。
