Laboratório de Neuroquímica e Neurofarmacologia, Departamento de Farmacologia, Instituto de Ciências Biológicas, Universidade Federal de Goiás, Goiânia, Goiás 74690-900, Brazil.
Laboratório de Cromatografia e Espectrometria de Massas, Instituto de Química, Universidade Federal de Goiás, Goiânia, Goiás 74690-900, Brazil.
Neuroscience. 2020 Feb 1;426:1-12. doi: 10.1016/j.neuroscience.2019.11.014. Epub 2019 Nov 27.
Vascular dementia (VD) is a major cognitive disorder originated from a blood flow disruption in the brain. This process leads to chronic cerebral ischemia that deeply affects neuronal tissues and lipid homeostasis. The understanding of cerebral lipid dynamics during chronic ischemia can reveal biomarkers and novel pharmacological targets for the treatment of VD. In this study, we used the Desorption Electrospray Ionization - imaging mass spectrometry (DESI-IMS) technique to map lipids in the rat brain tissues after bilateral common carotid artery occlusion (BCCAO) rat model of chronic cerebral hypoperfusion. The brain imaging enabled the detection of differences in lipids from ischemic and non-ischemic brains. The analysis demonstrated that arachidonic acid (ARA), docosahexaenoic acid (DHA), dihomo-γ-linolenic acid, hydroxyeicosatetraenoic (HETE)-Ala and glycerophosphoethanolamine levels were significantly reduced in the hippocampus and cortex of animals submitted to BCCAO model when compared to control animals. Decanoic acid was increased after 30 days of BCCAO model. Partial least squares discriminant analysis (PLS-DA) could discriminate between BCCAO group and the control group, in which γ-linolenic acid (m/z 277) ion and stearic acid (m/z 283) had the highest discrimination potential. Taken together, these findings indicate that lipid dynamics are altered in chronic ischemia-induced by BCCAO in rats and indicate potential biomarkers and pharmacological targets for VD.
血管性痴呆（VD）是一种源于大脑血流紊乱的主要认知障碍。这一过程导致慢性脑缺血，严重影响神经元组织和脂质稳态。了解慢性缺血期间的大脑脂质动态变化可以揭示 VD 的生物标志物和新的药理学靶点。在这项研究中，我们使用解吸电喷雾电离-成像质谱（DESI-IMS）技术对慢性脑低灌注大鼠双侧颈总动脉闭塞（BCCAO）模型的脑组织中的脂质进行成像。脑成像能够检测到缺血和非缺血脑组织中脂质的差异。分析表明，与对照组相比，BCCAO 模型动物的海马体和皮质中花生四烯酸（ARA）、二十二碳六烯酸（DHA）、二同型-γ-亚麻酸、羟二十碳四烯酸（HETE）-Ala 和甘油磷酸乙醇胺水平显著降低。癸酸在 BCCAO 模型 30 天后增加。偏最小二乘判别分析（PLS-DA）能够区分 BCCAO 组和对照组，其中γ-亚麻酸（m/z 277）离子和硬脂酸（m/z 283）具有最高的判别潜力。综上所述，这些发现表明 BCCAO 诱导的大鼠慢性缺血中脂质动态发生改变，并为 VD 提供了潜在的生物标志物和药理学靶点。
