Djite Moustapha, Chao de la Barca Juan Manuel, Bocca Cinzia, Gaye Ndiaga Matar, Barry Néné Oumou Kesso, Mbacke Mame Ndoumbé, Cissé Ousmane, Kandji Pape Matar, Thioune Ndèye Marème, Coly-Gueye Najah Fatou, Ndour El Hadji Malick, Gueye-Tall Fatou, Diop Amadou Gallo, Simard Gilles, Mirebeau-Prunier Delphine, Gueye Papa Madieye, Reynier Pascal
Laboratoire de Biochimie Pharmaceutique, Faculté de Médecine, Pharmacie, Université Cheikh Anta Diop, Dakar 2238, Senegal.
Laboratoire de Biochimie, Centre Hospitalier National Universitaire (CHNU) de FANN, Dakar 45701, Senegal.
Antioxidants (Basel). 2023 Dec 29;13(1):60. doi: 10.3390/antiox13010060.
Metabolomics is a powerful data-driven tool for in-depth biological phenotyping that could help identify the specific metabolic profile of cryptogenic strokes, for which no precise cause has been identified. We performed a targeted quantitative metabolomics study in West African patients who had recently suffered an ischemic stroke, which was either cryptogenic ( = 40) or had a clearly identified cause ( = 39), compared to a healthy control group ( = 40). Four hundred fifty-six metabolites were accurately measured. Multivariate analyses failed to reveal any metabolic profile discriminating between cryptogenic ischemic strokes and those with an identified cause but did show superimposable metabolic profiles in both groups, which were clearly distinct from those of healthy controls. The blood concentrations of 234 metabolites were significantly affected in stroke patients compared to controls after the Benjamini-Hochberg correction. Increased methionine sulfoxide and homocysteine concentrations, as well as an overall increase in saturation of fatty acids, were indicative of acute oxidative stress. This signature also showed alterations in energetic metabolism, cell membrane integrity, monocarbon metabolism, and neurotransmission, with reduced concentrations of several metabolites known to be neuroprotective. Overall, our results show that cryptogenic strokes are not pathophysiologically distinct from ischemic strokes of established origin, and that stroke leads to intense metabolic remodeling with marked oxidative and energetic stresses.
代谢组学是一种强大的数据驱动工具，用于深入的生物学表型分析，有助于识别不明原因卒中的特定代谢谱，这类卒中的确切病因尚未明确。我们对最近发生缺血性卒中的西非患者进行了一项靶向定量代谢组学研究，其中40例为不明原因缺血性卒中，39例病因明确，另有40例作为健康对照组。准确测量了456种代谢物。多变量分析未能揭示不明原因缺血性卒中和病因明确的卒中之间存在任何可区分的代谢谱，但显示两组的代谢谱可叠加，且明显不同于健康对照组。经本雅明尼-霍奇伯格校正后，与对照组相比，卒中患者血液中234种代谢物的浓度受到显著影响。甲硫氨酸亚砜和同型半胱氨酸浓度升高，以及脂肪酸饱和度总体增加均表明存在急性氧化应激。这一特征还显示了能量代谢、细胞膜完整性、一碳代谢和神经传递的改变，几种已知具有神经保护作用的代谢物浓度降低。总体而言，我们的结果表明，不明原因卒中在病理生理学上与已知病因的缺血性卒中并无差异，且卒中会导致强烈的代谢重塑，并伴有明显的氧化应激和能量应激。
