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脑内注射大麻二酚诱导的神经保护作用部分与短暂性局灶性脑缺血中的TNF-α/TNFR1/NF-кB通路相关。

Intra-cerebral cannabidiol infusion-induced neuroprotection is partly associated with the TNF-α/TNFR1/NF-кB pathway in transient focal cerebral ischaemia.

作者信息

Khaksar Sepideh, Bigdeli Mohammad Reza

机构信息

a Department of Physiology, Faculty of Life Sciences and Biotechnology , Shahid Beheshti University , Tehran , Iran.

出版信息

Brain Inj. 2017;31(13-14):1932-1943. doi: 10.1080/02699052.2017.1358397. Epub 2017 Sep 5.

Abstract

BACKGROUND

Stroke is a neurological disease, which, in addition to high mortality, imposes many financial and mental burdens on families and the society. The main objective of this study was to investigate the effect of cannabidiol (CBD) on one of the major inflammatory pathways in cerebral ischaemia.

METHOD

Using stereotaxic surgery, the cannula was implanted into the right lateral ventricle of rats. CBD (50, 100, and 200 ng/rat; i.c.v.) was administrated for five consecutive days. After pretreatment, the rats were subjected to 60 min of right middle cerebral artery occlusion (MCAO). After 24 h, neurological deficits score, infarct volume, brain oedema, and blood-brain barrier (BBB) permeability in total, core, and penumbra areas were assessed. The expression of tumour necrosis factor alfa (TNF-α), tumour necrosis factor receptor 1 (TNFR1), and nuclear factor-kappa B (NF-кB) in the mentioned regions was also studied.

RESULTS

Administration of CBD (100 and 200 ng/rat) caused a significant reduction in infarction, brain oedema, and BBB permeability compared with the vehicle-received group. Down-regulation of TNF-α, TNFR1, and NF-кB expression was also observed by CBD.

CONCLUSION

The results achieved in this study support the idea that CBD has a cerebroprotective effect (partly through suppression of TNF-α, TNFR1, and NF-кB) on ischaemic injury.

ABBREVIATIONS

CBD, cannabidiol; ANOVA, analysis of variance; PVDF, polyvinylidene difluoride; SDS-PAGE, sodium dodecyl sulphate polyacrylamide gel electrophoresis; SEM, standard error of mean.

摘要

背景

中风是一种神经疾病,除了死亡率高之外,还给家庭和社会带来许多经济和精神负担。本研究的主要目的是调查大麻二酚(CBD)对脑缺血主要炎症途径之一的影响。

方法

采用立体定向手术,将套管植入大鼠右侧脑室。连续五天给予CBD(50、100和200纳克/大鼠;脑室内注射)。预处理后,对大鼠进行60分钟的右侧大脑中动脉闭塞(MCAO)。24小时后,评估神经功能缺损评分、梗死体积、脑水肿以及总区域、核心区域和半暗带区域的血脑屏障(BBB)通透性。还研究了上述区域中肿瘤坏死因子α(TNF-α)、肿瘤坏死因子受体1(TNFR1)和核因子κB(NF-κB)的表达。

结果

与接受赋形剂的组相比,给予CBD(100和200纳克/大鼠)可显著降低梗死、脑水肿和BBB通透性。CBD还观察到TNF-α、TNFR1和NF-κB表达下调。

结论

本研究取得的结果支持以下观点,即CBD对缺血性损伤具有脑保护作用(部分通过抑制TNF-α、TNFR1和NF-κB)。

缩写

CBD,大麻二酚;ANOVA,方差分析;PVDF,聚偏二氟乙烯;SDS-PAGE,十二烷基硫酸钠聚丙烯酰胺凝胶电泳;SEM,平均标准误差。

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