Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study

Mondello, Stefania; Sandner, Viktor; Goli, Mona; Czeiter, Endre; Amrein, Krisztina; Kochanek, Patrick M.; Gautam, Sakshi; Cho, Byeong Gwan; Morgan, Ryan; Nehme, Ali; Fiumara, Giacomo; Eid, Ali H.; Barsa, Chloe; Haidar, Muhammad; Büki, András; Kobeissy, Firas; Mechref, Yehia

doi:10.1016/j.eclinm.2022.101494

Cited by 21 publications

(13 citation statements)

References 55 publications

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“…It has been reported by Mondello et al that the changes seen in serum glycans can be partially attributed to the biosynthetic and metabolic crisis after TBI, where in response to acute brain injury, multiple mechanisms consequence in mitochondrial dysfunction and increased oxidative stress with a shift from aerobic to anaerobic metabolism in neurons. [69] GalNAc, playing a keyrole in cell metabolism and signalling, has been further shown by the same researchers to compromise the blood brain barrier, triggering the metabolic disruption and the biochemical cascade following TBI cell damage, resulting in its release. Mondello et al have also recently identified a link between the observed alterations in the glycosylation biosynthetic pathways and the impact on the white matter damage and repair, and thereby clinical outcome, by assessing serum levels of 94 N-glycans post TBI.…”

Section: Resultsmentioning

confidence: 95%

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro‐Hydrodynamic Surface Molecular Lithography

Gomes,

Hin‐Chu,

Rickard

et al. 2024

Advanced Science

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Micro‐ and nanopatterning of materials, one of the cornerstones of emerging technologies, has transformed research capabilities in lab‐on‐a‐chip diagnostics. Herein, a micro‐ and nanolithographic method is developed, enabling structuring materials at the submicron scale, which can, in turn, accelerate the development of miniaturized platform technologies and biomedical sensors. Underpinning it is the advanced electro‐hydrodynamic surface molecular lithography, via inducing interfacial instabilities produces micro‐ and nanostructured substrates, uniquely integrated with synthetic surface recognition. This approach enables the manufacture of design patterns with tuneable feature sizes, which are functionalized via synthetic nanochemistry for highly sensitive, selective, rapid molecular sensing. The development of a high‐precision piezoelectric lithographic rig enables reproducible substrate fabrication with optimum signal enhancement optimized for functionalization with capture molecules on each micro‐ and nanostructured array. This facilitates spatial separation, which during the spectroscopic sensing, enables multiplexed measurement of target molecules, establishing the detection at minute concentrations. Subsequently, this nano‐plasmonic lab‐on‐a‐chip combined with the unconventional computational classification algorithm and surface enhanced Raman spectroscopy, aimed to address the challenges associated with timely point‐of‐care detection of disease‐indicative biomarkers, is utilized in validation assay for multiplex detection of traumatic brain injury indicative glycan biomarkers, demonstrating straightforward and cost‐effective micro‐ and nanoplatforms for accurate detection.

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Section: Resultsmentioning

confidence: 95%

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro‐Hydrodynamic Surface Molecular Lithography

Gomes,

Hin‐Chu,

Rickard

et al. 2024

Advanced Science

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“…Mondello et al (2022) found that 4 glycans were potentially correlated with TBI outcomes whereas two glycans signi cantly increased in patients with unfavorable outcome (GOSE ≤ 4) and 2 glycans increased in patients with favorable outcomes. This study also showed a correlation between the increased glycans and mass lesions and decompressive craniectomy [33].…”

Section: Discussionmentioning

confidence: 92%

Metabolomic profiles in serum predict global functional neurological outcome at 3 and 12 months and death at 3 months following severe traumatic brain injury

Banoei

Lee

Hutchison

et al. 2023

Preprint

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Background Prognostication is very important to clinicians and families during the early management of severe traumatic brain injury (sTBI), however, there are no gold standard biomarkers to determine prognosis in sTBI. As has been demonstrated in several diseases, early measurement of serum metabolomic profiles can be used as sensitive and specific biomarkers to predict outcome. Methods We prospectively enrolled adults with sTBI (Glasgow coma scale, GCS ≤ 8) in a multicenter Canadian TBI (CanTBI) study. Serum samples were drawn on the 1st and 4th day following injury for metabolomic profiling. The Glasgow outcome scale extended (GOSE) was collected at 3- and 12-months post-injury. Targeted direct infusion liquid chromatography tandem mass spectrometry (DI/LC-MS/MS) and untargeted proton nuclear magnetic resonance spectroscopy (1H-NMR) were used to profile serum metabolites. Multivariate analysis was used to determine the association between serum metabolomics and GOSE, dichotomized into favorable (GOSE 5–8) and unfavorable (GOSE 1–4), outcomes. Results Serum metabolic profiles on days 1 and 4 post-injury were highly predictive (Q2 > 0.4–0.5) and highly accurate (AUC > 0.99) to predict GOSE outcome at 3- and 12-months post-injury and mortality at 3 months. The metabolic profiles on day 4 were more predictive (Q2 > 0.55) than those measured on day 1 post-injury. Unfavorable outcomes were associated with considerable metabolite changes from day 1 to day 4 compared to favorable outcomes. Increased lysophosphatidylcholines, acylcarnitines, energy-related metabolites (glucose, lactate), aromatic amino acids and glutamate were associated with poor outcome and mortality. Discussion Metabolomic profiles were strongly associated with prognosis of GOSE outcome at 3 and 12 months and mortality following sTBI in adults. The current findings strongly support the use of serum metabolomics, which are shown to be better than clinical data, in determining prognosis in adults with sTBI in the early days post-injury. Our findings, however, require validation in a larger cohort of adults with sTBI before using in clinical practice.

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“…There is substantial evidence that aberrant glycosylation in serum glycoproteins can be linked to neurological and neurodegenerative disorders [ 19 , 50 ]. In this study, we observed changes in the glycome expression of serum low abundant glycoproteins that may represent MCI glycofingerprints, and therefore insights for AD development.…”

Section: Discussionmentioning

confidence: 99%

LC-MS/MS Isomeric Profiling of N-Glycans Derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Impairment Patients

et al. 2022

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Mild cognitive impairment (MCI) is an early stage of memory loss that affects cognitive abilities, such as language or virtual/spatial comprehension. This cognitive decline is mostly observed with the aging of individuals. Recently, MCI has been considered as a prodromal phase of Alzheimer’s disease (AD), with a 10–15% conversion rate. However, the existing diagnostic methods fail to provide precise and well-timed diagnoses, and the pathophysiology of MCI is not fully understood. Alterations of serum N-glycan expression could represent essential contributors to the overall pathophysiology of neurodegenerative diseases and be used as a potential marker to assess MCI diagnosis using non-invasive procedures. Herein, we undertook an LC-MS/MS glycomics approach to determine and characterize potential N-glycan markers in depleted blood serum samples from MCI patients. For the first time, we profiled the isomeric glycome of the low abundant serum glycoproteins extracted from serum samples of control and MCI patients using an LC-MS/MS analytical strategy. Additionally, the MRM validation of the identified data showed five isomeric N-glycans with the ability to discriminate between healthy and MCI patients: the sialylated N-glycans GlcNAc5,Hex6,Neu5Ac3 and GlcNAc6,Hex7,Neu5Ac4 with single AUCs of 0.92 and 0.87, respectively, and a combined AUC of 0.96; and the sialylated-fucosylated N-glycans GlcNAc4,Hex5,Fuc,Neu5Ac, GlcNAc5,Hex6,Fuc,Neu5Ac2, and GlcNAc6,Hex7,Fuc,Neu5Ac3 with single AUCs of 0.94, 0.67, and 0.88, respectively, and a combined AUC of 0.98. According to the ingenuity pathway analysis (IPA) and in line with recent publications, the identified N-glycans may play an important role in neuroinflammation. It is a process that plays a fundamental role in neuroinflammation, an important process in the progression of neurodegenerative diseases.

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Exploring serum glycome patterns after moderate to severe traumatic brain injury: A prospective pilot study

Cited by 21 publications

References 55 publications

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro‐Hydrodynamic Surface Molecular Lithography

Advanced Tuneable Micronanoplatforms for Sensitive and Selective Multiplexed Spectroscopic Sensing via Electro‐Hydrodynamic Surface Molecular Lithography

Metabolomic profiles in serum predict global functional neurological outcome at 3 and 12 months and death at 3 months following severe traumatic brain injury

LC-MS/MS Isomeric Profiling of N-Glycans Derived from Low-Abundant Serum Glycoproteins in Mild Cognitive Impairment Patients

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