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急性甲基苯丙胺处理和创伤性脑损伤后大鼠血清中促炎和抗炎细胞因子的升高。

Elevation of Pro-inflammatory and Anti-inflammatory Cytokines in Rat Serum after Acute Methamphetamine Treatment and Traumatic Brain Injury.

机构信息

Department of Biochemistry and Molecular Genetics, Faculty of Medicine, American University of Beirut, Beirut, Lebanon.

Program for Neurotrauma, Neuroproteomics, and Biomarkers Research, Gainesville, FL, USA.

出版信息

J Mol Neurosci. 2022 Jan;72(1):158-168. doi: 10.1007/s12031-021-01886-8. Epub 2021 Sep 20.

Abstract

The use of methamphetamine (METH) is a growing worldwide epidemic that bears grave societal implications. METH is known to exert its neurotoxic effects on the dopaminergic and serotonergic systems of the brain. In addition to this classical studied mechanism of damage, findings from our laboratory and others have shown that acute METH treatment and mechanical injury, i.e. traumatic brain injury (TBI), share common cell injury mechanism(s). Since neuro-inflammation is a signature event in TBI, we hypothesize that certain cytokine levels might also be altered in rat brain exposed to an acute METH insult. In this study, using a cytokine antibody array chip, we evaluated the serum levels of 19 cytokines in rats 24 h after exposure to a 40 mg/kg acute regimen of METH. Data were compared to rats subjected to experimental TBI using the controlled cortical impact (CCI) injury model and saline controls. Sandwich ELISA method was used to further validate some of the findings obtained from the antibody cytokine array. We confirmed that three major inflammatory-linked cytokines (IL-1β, IL-6, and IL-10) were elevated in the METH and TBI groups compared to the saline group. Such finding suggests the involvement of an inflammatory process in these brain insults, indicating that METH use is, in fact, a stressor to the immune system where systemic involvement of an altered cytokine profile may play a major role in mediating chemical brain injury after METH use.

摘要

冰毒(METH)的使用是一种在全球范围内不断增长的流行趋势,对社会产生了严重影响。METH 已知会对大脑的多巴胺能和 5-羟色胺能系统产生神经毒性作用。除了这种经典的损伤机制外,我们实验室和其他实验室的研究结果表明,急性 METH 处理和机械损伤(即创伤性脑损伤(TBI))共享共同的细胞损伤机制。由于神经炎症是 TBI 的标志性事件,我们假设在急性 METH 损伤暴露的大鼠大脑中,某些细胞因子水平也可能发生改变。在这项研究中,我们使用细胞因子抗体芯片评估了大鼠在暴露于 40mg/kg 急性 METH 方案后 24 小时的血清中 19 种细胞因子的水平。将数据与使用皮质撞击(CCI)损伤模型和盐水对照的实验性 TBI 大鼠进行比较。夹心 ELISA 法用于进一步验证抗体细胞因子阵列获得的部分发现。我们证实,与盐水组相比,METH 和 TBI 组三种主要的炎症相关细胞因子(IL-1β、IL-6 和 IL-10)升高。这种发现表明炎症过程参与了这些大脑损伤,表明 METH 的使用实际上是对免疫系统的一种应激源,全身细胞因子谱的改变可能在介导 METH 使用后的化学性脑损伤中发挥主要作用。

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