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Purinergic Astrocyte Signaling Driven by TNF-α After Cannabidiol Administration Restores Normal Synaptic Remodeling Following Traumatic Brain Injury

神经保护 谷氨酸受体 星形胶质细胞 创伤性脑损伤 神经科学 神经炎症 药理学 神经传递 医学 生物 中枢神经系统 内科学 受体 炎症 精神科
作者
Tenghan Ling,Aiping Yin,Yan Cao,Jiali Li,Hengxi Li,Ying Zhou,Xiaobing Guo,Jinghui Li,Ruilin Zhang,Haiying Wu,Ping Li
出处
期刊:Neuroscience [Elsevier]
卷期号:545: 31-46 被引量:1
标识
DOI:10.1016/j.neuroscience.2024.03.002
摘要

Traumatic brain injury (TBI) is a prevalent form of cranial trauma that results in neural conduction disruptions and damage to synaptic structures and functions. Cannabidiol (CBD), a primary derivative from plant-based cannabinoids, exhibits a range of beneficial effects, including analgesic, sedative, anti-inflammatory, anticonvulsant, anti-anxiety, anti-apoptotic, and neuroprotective properties. Nevertheless, the effects of synaptic reconstruction and the mechanisms underlying these effects remain poorly understood. TBI is characterized by increased levels of tumor necrosis factor-alpha (TNF-α), a cytokine integral for the modulation of glutamate release by astrocytes. In the present study, the potential of CBD in regulating aberrant glutamate signal transmission in astrocytes following brain injury, as well as the underlying mechanisms involved, were investigated using immunofluorescence double staining, enzyme-linked immunosorbent assay (ELISA), western blot analysis, hematoxylin and eosin (H&E) staining, Nissl staining, transmission electron microscopy, and RT-qPCR. In this study, we examined the impact of CBD on neuronal synapses, focusing on the TNF-α-driven purinergic signaling pathway. Specifically, our research revealed that CBD pretreatment effectively reduced the secretion of TNF-α induced by astrocyte activation following TBI. This reduction inhibited the interaction between TNF-α and P2Y1 receptors, leading to a decrease in the release of neurotransmitters, including Ca2+ and glutamate, thereby initiating synaptic remodeling. Our study showed that CBD exhibits significant therapeutic potential for TBI-related synaptic dysfunction, offering valuable insights for future research and more effective TBI treatments. Further exploration of the potential applications of CBD in neuroprotection is required to develop innovative clinical strategies.
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