Targeted metabolomics reveals serum changes of amino acids in mild to moderate ischemic stroke and stroke mimics

Abstract

BackgroundThe pathophysiological processes linked to an acute ischemic stroke (IS) can be reflected in the circulating metabolome. Amino acids (AAs) have been demonstrated to be one of the most significant metabolites that can undergo significant alteration after a stroke.MethodsWe sought to identify the potential biomarkers for the early detection of IS using an extensive targeted technique for reliable quantification of 27 different AAs based on ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). A cohort with 216 participants was enrolled, including 70 mild to moderate ischemic stroke patients (National Institutes of Health Stroke Scale < 15, MB group), 76 stroke mimics (MM group) and 70 healthy controls (NC group).ResultsIt was found that upon comparing MB and MM to control patients, AAs shifts were detected via partial least squares discrimination analysis (PLS-DA) and pathway analysis. Interestingly, MB and MM exhibited similar AAs pattern. Moreover, ornithine, asparagine, valine, citrulline, and cysteine were identified for inclusion in a biomarker panel for early-stage stroke detection based upon an AUC of 0.968 (95% CI 0.924–0.998). Levels of ornithine were positively associated with infract volume, 3 months mRS score, and National Institutes of Health Stroke Scale (NIHSS) score in MB. In addition, a metabolites biomarker panel, including ornithine, taurine, phenylalanine, citrulline, cysteine, yielded an AUC of 0.99 (95% CI 0.966–1) which can be employed to effectively discriminate MM patients from control.ConclusionOverall, alternations in serum AAs are characteristic metabolic features of MB and MM. AAs could serve as promising biomarkers for the early diagnosis of MB patients since mild to moderate IS patients were enrolled in the study. The metabolism of AAs can be considered as a key indicator for both the prevention and treatment of IS.

Brain and serum metabolomic studies reveal therapeutic effects of san hua decoction in rats with ischemic stroke

“…Arginine and proline metabolism have been shown to be associated with axon regeneration, and arginine is a necessary raw material for axon regeneration ( 37 ). L-ornithine produced during its metabolism has recently been shown to be one of the biomarkers used for early detection of stroke ( 38 ). L-ornithine transcarbamylase deficiency leads to elevated ornithine levels, which in turn cause impaired urea cycling that can lead to stroke-like episodes ( 39 ), impaired mitochondrial function and reduced antioxidant capacity ( 40 ).…”

Searching for Metabolic Markers of Stroke in Human Plasma via NMR Analysis

“…In humans, increased plasma Asn levels have been associated with the acute stage of ischaemic stroke but not the chronic stage [20]. Furthermore, targeted metabolomics studies using UPLC-MS/MS in 286 patients aged 63 to 65 years revealed increased serum Asn in mild to moderate ischaemic stroke [22]. Our results show an increase in Asn in elderly people from the LSR to HSR group and from the MSR to HSR group, suggesting that Asn increases before the stroke, and not immediately after the vascular event.…”

“…Some studies on ischaemic stroke using NMR and LC-MS have detected increased levels of asparagine and formate after the occurrence of stroke [19][20][21][22][23]. Some authors have suggested the involvement of pathways related to oxidative stress, such as the homocysteine metabolism and the formation of reactive oxygen species [24,25].…”