Department of Neurology, College of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma, USA; Oklahoma Center for Neuroscience, University of Oklahoma Health Sciences Center, USA.
Physiology, College of Medicine, University of Oklahoma Health Sciences Center, USA.
J Stroke Cerebrovasc Dis. 2023 Aug;32(8):107211. doi: 10.1016/j.jstrokecerebrovasdis.2023.107211. Epub 2023 Jun 16.
Acute Ischemic Stroke (AIS), a major cause of disability, was previously associated with multiple metabolomic changes, but many findings were contradictory. Case-control and longitudinal study designs could have played a role in that. To clarify metabolomic changes, we performed a simultaneous comparison of ischemic stroke metabolome in acute, chronic stages of stroke and controls.
Through the nuclear magnetic resonance (NMR) platform, we evaluated 271 serum metabolites from a cohort of 297 AIS patients in acute and chronic stages and 159 controls. We used Sparse Partial Least Squares-Discriminant analysis (sPLS-DA) to evaluate group disparity; multivariate regression to compare metabolome in acute, chronic stages of stroke and controls; and mixed regression to compare metabolome acute and chronic stages of stroke. We applied false discovery rate (FDR) to our calculations.
The sPLS-DA revealed separation of the metabolome in acute, chronic stages of stroke and controls. Regression analysis identified 38 altered metabolites. Ketones, branched-chain amino acids (BCAAs), energy, and inflammatory compounds were mostly elevated, while alanine and glutamine were decreased in the acute stage. These metabolites declined/increased in the chronic stage, often to the same levels as in controls. Levels of fatty acids, phosphatidylcholines, phosphoglycerides, and sphingomyelins did not change between acute and chronic stages, but were different comparing to controls.
Our pilot study identified metabolites associated with acute stage of ischemic stroke and those that are altered in stroke patients comparing to controls regardless of stroke acuity. Future investigation in a larger independent cohort is needed to validate these findings.
急性缺血性脑卒中（AIS）是导致残疾的主要原因，先前与多种代谢组学变化有关，但许多发现相互矛盾。病例对照和纵向研究设计可能在其中起到了一定作用。为了阐明代谢组学变化，我们同时比较了急性和慢性阶段缺血性脑卒中患者以及对照组的代谢组。
通过核磁共振（NMR）平台，我们评估了 297 例急性和慢性 AIS 患者以及 159 例对照者的 271 种血清代谢物。我们使用稀疏偏最小二乘判别分析（sPLS-DA）来评估组间差异；多元回归分析比较急性和慢性阶段脑卒中以及对照组的代谢组；混合回归分析比较急性和慢性阶段脑卒中的代谢组。我们对计算结果应用了错误发现率（FDR）校正。
sPLS-DA 揭示了急性和慢性阶段脑卒中以及对照组代谢组的分离。回归分析确定了 38 种代谢物发生了改变。在急性阶段，酮体、支链氨基酸（BCAAs）、能量和炎症化合物升高，而丙氨酸和谷氨酰胺降低。这些代谢物在慢性阶段下降/升高，通常与对照组水平相当。脂肪酸、磷脂酰胆碱、磷酸甘油酯和神经鞘磷脂在急性和慢性阶段之间没有变化，但与对照组不同。
我们的初步研究确定了与急性缺血性脑卒中阶段相关的代谢物以及与对照组相比，在脑卒中患者中发生改变的代谢物，无论脑卒中的严重程度如何。需要在更大的独立队列中进行进一步研究以验证这些发现。
