Department of Neurology, Leiden University Medical Center, 2300 RC, Leiden, The Netherlands.
Maastricht MultiModal Molecular Imaging (M4I) Institute, Division of Imaging Mass Spectrometry, Maastricht University, 6229 ER, Maastricht, The Netherlands.
Sci Rep. 2019 Jan 31;9(1):1090. doi: 10.1038/s41598-018-37612-5.
Detecting different lipid profiles in early infarct development may give an insight on the fate of compromised tissue. Here we used Mass Spectrometry Imaging to identify lipids at 4, 8 and 24 hours after ischemic stroke in mice, induced by transient middle cerebral artery occlusion (tMCAO). Combining linear transparency overlay, a clustering pipeline and spatial segmentation, we identified three regions: infarct core, penumbra (i.e. comprised tissue that is not yet converted to core), and surrounding healthy tissue. Phosphatidylinositol 4-phosphate (m/z = 965.5) became visible in the penumbra 24 hours after tMCAO. Infarct evolution was shown by 2D-renderings of multiple phosphatidylcholine (PC) and Lyso-PC isoforms. High-resolution Secondary Ion Mass Spectrometry, to evaluate sodium/potassium ratios, revealed a significant increase in sodium and a decrease in potassium species in the ischemic area (core and penumbra) compared to healthy tissue at 24 hours after tMCAO. In a transgenic mouse model with an enhanced susceptibility to ischemic stroke, we found a more pronounced discrimination in sodium/potassium ratios between penumbra and healthy regions. Insight in changes in lipid profiles in the first hours of stroke may guide the development of new prognostic biomarkers and novel therapeutic targets to minimize infarct progression.
在早期梗死发展中检测不同的脂质谱可能有助于了解受损组织的命运。在这里，我们使用质谱成像技术在小鼠短暂性大脑中动脉闭塞（tMCAO）后 4、8 和 24 小时检测到缺血性中风后的脂质。结合线性透明叠加、聚类管道和空间分割，我们确定了三个区域：梗死核心、半影区（即尚未转化为核心的组织）和周围健康组织。在 tMCAO 后 24 小时，磷脂酰肌醇 4-磷酸（m/z = 965.5）在半影区可见。通过多个磷酯酰胆碱（PC）和溶血磷酯酰胆碱（Lyso-PC）异构体的 2D 渲染显示了梗死的演变。评估钠/钾比的高分辨率二次离子质谱显示，与 tMCAO 后 24 小时的健康组织相比，缺血区（核心和半影区）的钠含量显著增加，钾含量显著降低。在对缺血性中风易感性增强的转基因小鼠模型中，我们发现钠/钾比在半影区和健康区之间的区分更加明显。对中风后最初几小时内脂质谱变化的深入了解可能有助于开发新的预后生物标志物和新的治疗靶点，以最大限度地减少梗死进展。
