Granulocyte Colony-Stimulating Factor Enhances Brain Repair Following Traumatic Brain Injury Without Requiring Activation of Cannabinoid Receptors.
Granulocyte Colony-Stimulating Factor Enhances Brain Repair Following Traumatic Brain Injury Without Requiring Activation of Cannabinoid Receptors.
复制标题
粒细胞集落刺激因子可增强脑外伤后的脑修复，而不需要激活大麻素受体。
DOI：
10.1089/can.2019.0090
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发表时间：
2021
影响因子：
3.8
通讯作者：
Sanchez-Ramos,Juan
中科院分区：
文献类型：
--
作者：
Song,Shijie;Kong,Xiaoyuan;Borlongan,Cesar;Sava,Vasyl;Sanchez-Ramos,Juan
引言：用粒细胞集落刺激因子（G-CSF）治疗创伤性脑损伤（TBI）已被证明可通过对神经细胞的直接神经营养作用和调节炎症反应来增强脑修复。TBI后大麻素的管理也被报道，以提高脑修复通过类似mechanism.Objectives：本研究的主要目的是测试的假设，即G-CSF介导的脑修复通过与endocannabinoid system.Methods和结果：（i）小鼠进行控制皮质撞击（CCI）单独或在存在选择性大麻素受体1（CB 1-R）或大麻素受体2（CB 2-R）激动剂和拮抗剂的G-CSF治疗3天。创伤导致皮质、纹状体和海马中CB 1-R的表达减少，CB 2-R的表达增加。皮质和纹状体水平的主要内源性大麻素配体，2-花生四烯酸甘油，也增加了CCI。TBI后给予造血细胞因子G-CSF可减轻或逆转创伤诱导的CB 1-R下调和CB 2-R上调。用CB 1-R激动剂（WIN 55）或CB 2-R激动剂（HU 308）处理模拟G-CSF的作用。(ii)CB 1-R或CB 2-R的药理学阻断在预防G-CSF的减轻或逆转创伤诱导的这些receptors.Conclusions的改变中是无效的：这些结果表明，介导G-CSF亚急性效应的细胞和分子机制不依赖于CB 1或CB 2受体的激活。必须谨慎接受选择性CB受体拮抗剂未能阻止该模型中G-CSF的作用。CB受体拮抗剂可以与其他CB和非CB受体相互作用。CB受体在该TBI模型中的作用的研究将需要用CB 1-R和CB 2-R敲除小鼠进行研究，以避免CB受体药剂与其他受体的非特异性相互作用。
Introduction:Treatment of traumatic brain injury (TBI) with granulocyte colony-stimulating factor (G-CSF) has been shown to enhance brain repair by direct neurotrophic actions on neural cells and by modulating the inflammatory response. Administration of cannabinoids after TBI has also been reported to enhance brain repair by similar mechanisms.Objectives:The primary objective of this study was to test the hypothesis that G-CSF mediates brain repair by interacting with the endocannabinoid system.Methods and Results:(i) Mice that underwent controlled cortical impact (CCI) were treated with G-CSF for 3 days either alone or in the presence of selective cannabinoid receptor 1 (CB1-R) or cannabinoid receptor 2 (CB2-R) agonists and antagonists. The trauma resulted in decreased expression of CB1-R and increased expression of CB2-R in the cortex, striatum, and hippocampus. Cortical and striatal levels of the major endocannabinoid ligand, 2-arachidonoyl-glycerol, were also increased by the CCI. Administration of the hematopoietic cytokine, G-CSF, following TBI, resulted in mitigation or reversal of trauma-induced CB1-R downregulation and CB2-R upregulation in the three brain regions. Treatment with CB1-R agonist (WIN55) or CB2-R agonist (HU308) mimicked the effects of G-CSF. (ii) Pharmacological blockade of CB1-R or CB2-R was not effective in preventing G-CSF's mitigation or reversal of trauma-induced alterations in these receptors.Conclusions:These results suggest that cellular and molecular mechanisms that mediate subacute effects of G-CSF do not depend on activation of CB1 or CB2 receptors. Failure of selective CB receptor antagonists to prevent the effects of G-CSF in this model has to be accepted with caution. CB receptor antagonists can interact with other CB and non-CB receptors. Investigation of the role of CB receptors in this TBI model will require studies with CB1-R and in CB2-R knockout mice to avoid nonspecific interaction of CB receptor agents with other receptors.
Omega-3 内源性大麻素环氧化物是新型抗炎和止痛脂质代谢物 (FS15-01-19)。
影响因子：
4.8
作者：
A. Das;Josephine E Watson;Lauren N Carnevale;William R Arnold
通讯作者：
William R Arnold
影响因子：
2.8
作者：
Song, Shijie;Kong, Xiaoyuan;Sanchez-Ramos, Juan
通讯作者：
Sanchez-Ramos, Juan
影响因子：
5.3
作者：
Katona, I;Rancz, EA;Freund, TF
通讯作者：
Freund, TF