血脑屏障
神经保护
星形胶质细胞
乳酸脱氢酶
药理学
促炎细胞因子
脑缺血
化学
生物
内科学
医学
免疫学
缺血
内分泌学
炎症
生物化学
中枢神经系统
酶
作者
Nicole Stone,Timothy J. England,Saoirse E. O'Sullivan
出处
期刊:Cannabis and cannabinoid research
[Mary Ann Liebert]
日期:2021-03-17
卷期号:6 (4): 315-326
被引量:8
标识
DOI:10.1089/can.2020.0159
摘要
Background and Objectives: Preclinical studies have shown cannabidiol is protective in models of ischemic stroke. Based on results from our recent systematic review, we investigated the effects of two promising neuroprotective phytocannabinoids, cannabigerol (CBG) and cannabidivarin (CBDV), on cells of the blood-brain barrier (BBB), namely human brain microvascular endothelial cells (HBMECs), pericytes, and astrocytes. Experimental Approach: Cultures were subjected to oxygen-glucose deprivation (OGD) protocol to model ischemic stroke and cell culture medium was assessed for cytokines and adhesion molecules post-OGD. Astrocyte cell lysates were also analyzed for DNA damage markers. Antagonist studies were conducted where appropriate to study receptor mechanisms. Results: In astrocytes CBG and CBDV attenuated levels of interleukin-6 (IL-6) and lactate dehydrogenase (LDH), whereas CBDV (10 nM-10 μM) also decreased vascular endothelial growth factor (VEGF) secretion. CBDV (300 nM-10 μM) attenuated levels of monocyte chemoattractant protein (MCP)-1 in HBMECs. In astrocytes, CBG decreased levels of DNA damage proteins, including p53, whereas CBDV increased levels of DNA damage markers. Antagonists for CB1, CB2, PPAR-γ, PPAR-α, 5-HT1A, and TRPV1 had no effect on CBG (3 μM) or CBDV (1 μM)-mediated decreases in LDH in astrocytes. GPR55 and GPR18 were partially implicated in the effects of CBDV, but no molecular target was identified for CBG. Conclusions: We show that CBG and CBDV were protective against OG mediated injury in three different cells that constitute the BBB, modulating different hallmarks of ischemic stroke pathophysiology. These data enhance our understanding of the protective effects of CBG and CBDV and warrant further investigation into these compounds in ischemic stroke. Future studies should identify other possible neuroprotective effects of CBG and CBDV and their corresponding mechanisms of action.
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