Glycans as Potential Diagnostic Markers of Traumatic Brain Injury

Abstract

The diagnosis of mild traumatic brain injury (TBI) is challenging in the acute setting because the symptoms are nonspecific and often transient, or they develop with a delay. In these cases, the criteria for acute head imaging are frequently not fulfilled. This may lead to missed diagnoses in emergency care. There is a need for developing a rapid diagnostic test to verify the presence of TBI using body fluids. Blood, urine, and saliva samples from 11 adult patients (mean age 64 years, SD 24 years) with acute and clinically diagnosed TBI, and 12 healthy volunteers were collected at Turku University Hospital during a period of 5 months. The injuries necessitated hospitalization for at least one day. The TBIs were classified mild in nine cases and severe in two cases. The mean period between the trauma and the time for obtaining the samples was 27 h, SD 11 h. The samples were analyzed in an ISO-certified laboratory for the number of lectin-bound glycan molecules indicating destruction of nerve tissue. The screening was performed on several possible glycans for binding, and the measurement by degree of fluorescence. In the analysis, the group of patients with TBI was compared with healthy volunteers. The results showed a significant decrease (p < 0.05, Wilcoxon rank–sum two-sided test) in the level of two glycans in plasma, but no significant increase for any glycan; in saliva, one glycan showed a significant increase in the TBI group; in urine, three glycans were significantly different between the groups (one showed an increase, whereas two showed a decrease). The results support the idea of conducting more research on how diagnostic glycans could be detected in body fluids after TBI. As a proof-of-concept, significant changes in the concentration of five glycans were found in plasma, saliva, and urine between TBI patients and healthy controls. This may enable the development of a rapid body fluid-based point-of-care test to identify patients with TBI after a head injury.

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

“…First, a benzyl-terminated self-assembled monolayer (ST75), with a benzene ring termination, which does not interact with the target molecules (i.e., no affinity). Second, a benzoboroxole self-assembled monolayer (ST95), which reversibly forms covalent bonds with the carbohydrate hydroxyl groups [42,58,59] and has the same functional group as the boronic acid complex, yet without the specific conformation of the "lock-and-key" function (i.e., lacking the spatial specificity). Surface molecular selective recognition of glycans was subsequently established via a direct self-assembled acrylamide terminated monolayer, a target glycan and the N', N'-bis-(acryloyl cystamine)-benzoboroxole carbohydrate complex (DSAC), which has the functional group-specifics for the analyte of interest and anchors the whole structure to the substrate.…”

“…Subsequently, the fabricated SMART EHSML platforms were assessed to detect TBI‐indicative glycan biomarkers, that is, GalNAc, Fuc6GlcNAc, Gal β 3GalNAc and Man α 3, first individually and then from a mixture. The chosen glycans have been recently measured from plasma and saliva samples with significant concentration changes post‐injury, which may relate to their excretion into the circulation following increased metabolism from damaged neurons, [ 59 ] as indicators of destruction of nerve tissue, signposting these as biomarkers for detecting early TBI onset. Following the molecular peak signatures corresponding to specific structural and composition information, blood plasma samples of healthy patients were spiked with the TBI‐indicative glycans (Figure S5 , Supporting Information) and analyzed with and without the spiked biomarker to test the recovery.…”

Glycans as Potential Diagnostic Markers of Traumatic Brain Injury in Children

“…Alterations in glycans have been shown to indicate TBI in adult patients [ 11 ]. The present study was conducted to collect clinical samples from children for the discovery of a novel biomarker for TBI.…”