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急性静脉注射甲基苯丙胺和 LPS 刺激促进 C57BL/6 小鼠白细胞浸润中枢神经系统。

Combination of acute intravenous methamphetamine injection and LPS challenge facilitate leukocyte infiltration into the central nervous system of C57BL/6 mice.

机构信息

Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY, USA.

Department of Biomedical Sciences, NYIT College of Osteopathic Medicine, New York Institute of Technology, Old Westbury, NY, USA; Department of Biological Sciences, The Border Biomedical Research Center, The University of Texas at El Paso, TX, USA.

出版信息

Int Immunopharmacol. 2019 Oct;75:105751. doi: 10.1016/j.intimp.2019.105751. Epub 2019 Jul 15.

Abstract

Methamphetamine (METH) is a stimulant of the central nervous system (CNS) that causes behavioral changes in users. METH is slowly cleared from brain tissue and its chronic use is neurotoxic. METH also alters the cellular and chemical components of inflammation. However, little is known about the effect of a single intravenous dose of METH followed by bacterial lipopolysaccharide (LPS) injection on cellular infiltration and cytokine release in brain tissue. Using a murine model of acute METH administration and flow cytometry, we found that combination of METH and LPS stimulate the infiltration of macrophages (F4/80cells) and neutrophils (Ly-6Gcells) into the CNS. Histological sections of the brainstem of METH-treated and LPS-challenged C57BL/6 mice demonstrated considerable leukocyte infiltration relative to untreated, LPS, and METH groups. Moreover, rodents treated with LPS alone or combined with METH showed elevated levels of pro-inflammatory cytokines mRNA in brain tissue. Our observations are important because recognizing neuroinflammatory changes after acute METH administration might help us to understand METH-induced neurotoxicity in users.

摘要

甲基苯丙胺(METH)是一种中枢神经系统(CNS)兴奋剂,会导致使用者的行为发生变化。METH 从脑组织中缓慢清除,其长期使用具有神经毒性。METH 还会改变炎症的细胞和化学组成部分。然而,人们对于单次静脉注射 METH 后注射细菌脂多糖(LPS)对脑组织中细胞浸润和细胞因子释放的影响知之甚少。使用急性 METH 给药的小鼠模型和流式细胞术,我们发现 METH 和 LPS 的组合刺激巨噬细胞(F4/80 细胞)和中性粒细胞(Ly-6G 细胞)浸润中枢神经系统。与未处理、LPS 和 METH 组相比,METH 处理和 LPS 挑战的 C57BL/6 小鼠脑干的组织学切片显示出相当数量的白细胞浸润。此外,单独用 LPS 或与 METH 联合处理的啮齿动物的脑组织中促炎细胞因子 mRNA 水平升高。我们的观察结果很重要,因为识别急性 METH 给药后神经炎症变化可能有助于我们了解使用者的 METH 诱导的神经毒性。

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