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创伤性脑损伤后大鼠脑脂质谱随时间变化的质谱成像

Mass spectrometry imaging of rat brain lipid profile changes over time following traumatic brain injury.

作者信息

Roux Aurelie, Muller Ludovic, Jackson Shelley N, Post Jeremy, Baldwin Katherine, Hoffer Barry, Balaban Carey D, Barbacci Damon, Schultz J Albert, Gouty Shawn, Cox Brian M, Woods Amina S

机构信息

Structural Biology Unit, Integrative Neuroscience Branch, NIH/NIDA-IRP, Baltimore, MD 21224, United States.

University Hospitals of Cleveland, Cleveland, OH 44106, United States.

出版信息

J Neurosci Methods. 2016 Oct 15;272:19-32. doi: 10.1016/j.jneumeth.2016.02.004. Epub 2016 Feb 10.

Abstract

BACKGROUND

Mild traumatic brain injury (TBI) is a common public health issue that may contribute to chronic degenerative disorders. Membrane lipids play a key role in tissue responses to injury, both as cell signals and as components of membrane structure and cell signaling. This study demonstrates the ability of high resolution mass spectrometry imaging (MSI) to assess sequences of responses of lipid species in a rat controlled cortical impact model for concussion.

NEW METHOD

A matrix of implanted silver nanoparticles was implanted superficially in brain sections for matrix-assisted laser desorption (MALDI) imaging of 50μm diameter microdomains across unfixed cryostat sections of rat brain. Ion-mobility time-of-flight MS was used to analyze and map changes over time in brain lipid composition in a rats after Controlled Cortical Impact (CCI) TBI.

RESULTS

Brain MS images showed changes in sphingolipids near the CCI site, including increased ceramides and decreased sphingomyelins, accompanied by changes in glycerophospholipids and cholesterol derivatives. The kinetics differed for each lipid class; for example ceramides increased as early as 1 day after the injury whereas other lipids changes occurred between 3 and 7 days post injury.

COMPARISON WITH EXISTING METHOD(S): Silver nanoparticles MALDI matrix is a sensitive new tool for revealing previously undetectable cellular injury response and remodeling in neural, glial and vascular structure of the brain.

CONCLUSIONS

Lipid biochemical and structural changes after TBI could help highlighting molecules that can be used to determine the severity of such injuries as well as to evaluate the efficacy of potential treatments.

摘要

背景

轻度创伤性脑损伤(TBI)是一个常见的公共卫生问题,可能会导致慢性退行性疾病。膜脂在组织对损伤的反应中起着关键作用,既是细胞信号,也是膜结构和细胞信号传导的组成部分。本研究展示了高分辨率质谱成像(MSI)在大鼠控制性皮质撞击脑震荡模型中评估脂质种类反应序列的能力。

新方法

将植入的银纳米颗粒基质表面植入脑切片中,用于对大鼠脑未固定低温恒温器切片上直径50μm的微区进行基质辅助激光解吸(MALDI)成像。离子迁移飞行时间质谱用于分析和绘制控制性皮质撞击(CCI)脑外伤后大鼠脑脂质成分随时间的变化。

结果

脑MS图像显示CCI部位附近鞘脂发生变化,包括神经酰胺增加和鞘磷脂减少,同时甘油磷脂和胆固醇衍生物也发生变化。每种脂质类别的动力学不同;例如,神经酰胺在损伤后1天就开始增加,而其他脂质变化发生在损伤后3至7天之间。

与现有方法的比较

银纳米颗粒MALDI基质是一种敏感的新工具,可揭示大脑神经、胶质和血管结构中以前无法检测到的细胞损伤反应和重塑。

结论

TBI后脂质生化和结构变化有助于突出可用于确定此类损伤严重程度以及评估潜在治疗效果的分子。

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