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Sensing and Assessment of Brain Injury
Published in Mark A. Mentzer, Mild Traumatic Brain Injury, 2020
Perhaps the best metric for mTBI diagnosis in the field explored thus far is the use of biomarkers, as they are suitable for point of care diagnostics. Biomarkers are defined (Biomarkers Definitions Working Group, 2001) as those with a “characteristic that is objectively measured and evaluated as an indicator of normal biological processes, pathogenic processes, or pharmacologic responses to a therapeutic intervention.” They may be implemented based on preliminary indications that mTBI may have occurred. Some key potential biomarkers follow along with their associations to a variety of cell damage mechanisms (Wang et al., 2015). S100B is a good example of a biomarker that exhibits not only in cerebral spinal fluid but can also be detected in blood.
Molecular Pathology
Published in Burkhard Madea, Asphyxiation, Suffocation,and Neck Pressure Deaths, 2020
Astrocytes are more resistant to hypoxic conditions than neurones. The S100 proteins have an A and B subunit and are small acidic calcium-binding proteins. S100B is highly specific for astrocytes, oligodendrocytes and ependymocytes in the central nervous system. Clinically, S100B seems to act as a serum marker of brain damage from cerebral injury and hypoxia/ischaemia. Li et al. [20] found that, in cases of asphyxiation due to neck compression, the number of astrocytes immunostained with anti-S100 or anti-GFAP was significantly decreased, compared with that for other asphyxiation and acute myocardial infarction. Reciprocally, serum S100B levels were significantly higher in asphyxiation by neck compression than in other types of asphyxiation. These observations imply that astrocytes and serum S100B would be available biomarkers for supporting the diagnosis of asphyxiation due to neck compression.
Biomarkers for Organophosphate Poisoning: Physiological and Pathological Responses
Published in Brian J. Lukey, James A. Romano, Salem Harry, Chemical Warfare Agents, 2019
Arik Eisenkraft, Avshalom Falk, Kevin G. McGarry Jr.
Three biomarkers of initial interest are S100B, brain-derived neurotrophic factor (BDNF), and UCH-L1. Recent work performed at the Battelle Memorial Institute has identified changes in circulating levels of S100B and UCH-L1 (and potentially BDNF) following a 1.20 × LD50 challenge of the NA soman (manuscript submitted for publication). S100B is a calcium-binding protein primarily produced by astrocytes in the CNS. This protein has been implicated in the development and maintenance of the nervous system, and changes in the levels of S100B are widely considered a relevant biomarker for damage/dysfunction of the CNS (Egea-Guerrero et al., 2012). Multiple studies have shown a positive correlation of elevated S100B levels with the severity of a head trauma and poor clinical outcomes (Leviton and Dammann, 2002; Raabe et al., 1999; Schultke et al., 2009; Van Eldik and Wainwright, 2003; Vos et al., 2010; Willoughby et al., 2004). Following an OP exposure, multiple studies indicate that S100B levels increase in rats exposed to chloropyrifos oxon (Bozkurt et al., 2010) and diisopropyl fluorophosphate (DFP) (Supasai, 2017). S100B levels have also been shown to be elevated and correlate with survival in humans exposed to various OPs (Yardan et al., 2013). Interestingly, the elevation of S100B appears to be region specific within the brain (Supasai, 2017). As discussed earlier, following an OP exposure, Ca2+ levels increase as a result of the opening of GluR ion channels, and thus, perhaps due to its function as a calcium-binding protein, S100B is upregulated following the CNS injury induced by an NA exposure.
S100B protein: general characteristics and pathophysiological implications in the Central Nervous System
Published in International Journal of Neuroscience, 2022
Ana Cristina Arrais, Lívia Helena M. F. Melo, Bianca Norrara, Marina Abuquerque B. Almeida, Kalina Fernandes Freire, Acydalia Madruga M. F. Melo, Lucidio Clebeson de Oliveira, Francisca Overlânia Vieira Lima, Rovena Clara G. J. Engelberth, Jeferson de Souza Cavalcante, Dayane Pessoa de Araújo, Fausto Pierdoná Guzen, Marco Aurelio M. Freire, José Rodolfo L. P. Cavalcanti
S100B is involved in regulatory activities both intra and extracellularly, exerting its biological function interacting with other proteins, directly influencing the activity of these cells. With respect to its intracellular actions, it acts making regulatory effects on cell proliferation, shape, and differentiation, as well as energetic metabolism (42), enzymatic activation via interaction with cytoplasmic cytoskeletal proteins such as glial fibrillar acid protein (GFAP) and CAPz (43), as well as protein phosphorylation, transcription and homeostasis of Ca2+ (21). GFAP, in particular, is a constitutive protein of macroglial cells in the CNS that regulates brain homeostasis in both normal and altered states. Since astrocytes are activated following disturbances in the normal physiology of the CNS (44–49), its regulation by S100B can be associated with an increase in the pro-inflammatory cytokines release through NF-kβ and p38 MAPK signaling (50).
Reliability of serum S100B measurement following mild traumatic brain injury: a comparison of assay measurements from two laboratories
Published in Brain Injury, 2020
Grant L. Iverson, Jussi P. Posti, Juha Öhman, Kaj Blennow, Henrik Zetterberg, Teemu Miikka Luoto
Venous blood samples were collected within 6 h of injury. Blood samples were centrifuged for 10 min at 10,000 rpm at room temperature. Part of the serum was analyzed at Tampere University Hospital (Tampere, Finland) as part of the hospital laboratory’s on-call services. The remaining serum was stored in Eppendorf tubes and immediately frozen at −70°C for future analysis. Serum S100B was measured at two independent centers (i) Tampere University Hospital (clinical laboratory), and (ii) approximately two years later at the Sahlgrenska University Hospital (research laboratory), Mölndal, Sweden using the same commercially available assay (Elecsys S100®; Roche Diagnostics, Penzberg, Germany) that has a measuring range of 0.015‑30 ug/L, lower limit of detection of 0.015 ug/L and lower limit of quantification of 0.02 ug/L. There was only one value for S100B that was computed to be below the lower limit of quantification when run by the lab in Mölndal (i.e., 0.005), and that value was retained for analyses. The lowest S100B value from the lab in Tampere was 0.04. The assays were run on a similar instrument (Cobas e601®; Roche Diagnostics, Penzberg, Germany). The blood samples were collected in Tampere between November 2015 and November 2016. The serum samples were analyzed in Gothenburg on the 12th of March 2018. The mean interval in which the serum was frozen was 23.9 months (SD = 2.9, Range = 17–27). All the serum samples were transferred in 20 kg of dry ice from Tampere to Mölndal by a courier. The samples analyzed in Mölndal underwent one cycle of freezing and thawing.
Proteomic examination of the neuroglial secretome: lessons for the clinic
Published in Expert Review of Proteomics, 2020
Jong-Heon Kim, Ruqayya Afridi, Won-Ha Lee, Kyoungho Suk
Most astrocytic tasks are mediated by the release of proteins and peptides, such as extracellular matrix proteins, growth factors, and proteases [44]. The secretion of proteins such as thrombospondins (TSPs 1-4) and hevin has already been characterized in in-vitro and in-vivo studies, highlighting the important role of astrocytes in maintaining neuronal integrity [45]. Various secreted and contact-dependent signals play crucial roles in the cooperative and dynamic interplay between neurons and astrocytes [46]. In a recent study, several astrocyte-secreted proteins that regulate neuronal development were identified. These results imply the importance of cholinergic stimulation of astrocytes in neuronal development through extracellular matrix proteins and proteases [47]. S100B, chiefly an astrocytic protein, is a calcium-dependent regulatory protein that regulates the functions of effector proteins in cells. The role of S100B has been characterized in a broad spectrum of neurological diseases ranging from inflammatory to degenerative conditions. Similar to C reactive protein (CRP), S100B could also be an important clinical biomarker of CNS injury and disease [48]. A total of 6,000 unique proteins were identified in astrocytic conditioned medium by Han et al. in 2014 [49]. The increased release of inflammatory proteins from D1A cells (astrocyte type I clone) highlights the diverse role played by astrocytes in maintaining brain homeostasis [49].