The S100B story: from biomarker to active factor in neural injury

Abstract

S100B is a Ca -binding protein mainly concentrated in astrocytes. Its levels in biological fluids (cerebrospinal fluid, peripheral and cord blood, urine, saliva, amniotic fluid) are recognized as a reliable biomarker of active neural distress. Although the wide spectrum of diseases in which the protein is involved (acute brain injury, neurodegenerative diseases, congenital/perinatal disorders, psychiatric disorders) reduces its specificity, its levels remain an important aid in monitoring the trend of the disorder. Mounting evidence now points to S100B as a Damage-Associated Molecular Pattern molecule which, when released at high concentration, through its Receptor for Advanced Glycation Endproducts, triggers tissue reaction to damage in a series of different neural disorders. This review addresses this novel scenario, presenting data indicating that S100B levels and/or distribution in the nervous tissue of patients and/or experimental models of different neural disorders, for which the protein is used as a biomarker, are directly related to the progress of the disease: acute brain injury (ischemic/hemorrhagic stroke, traumatic injury), neurodegenerative diseases (Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, multiple sclerosis), congenital/perinatal disorders (Down syndrome, spinocerebellar ataxia-1), psychiatric disorders (schizophrenia, mood disorders), inflammatory bowel disease. In many cases, over-expression/administration of the protein induces worsening of the disease, whereas its deletion/inactivation produces amelioration. This review points out that the pivotal role of the protein resulting from these data, opens the perspective that S100B may be regarded as a therapeutic target for these different diseases, which appear to share some common features reasonably attributable to neuroinflammation, regardless their origin.

Alterations of Astrocytes in the Context of Schizophrenic Dementia

“…S100B-immunopositive glia was elevated in paranoid as compared to residual schizophrenia patients (Steiner et al, 2008). There is evidence that S100B can be released by astrocytes in response to activation of 5-HT receptor, which means that an excess of serotonin can provoke the release of S100B, but this is opposed by serotonin and norepinephrine reuptake inhibitor in the hippocampus of rats (Michetti et al, 2019). Increased S100B expression can lead to metabolic disturbances in astrocytes and neurons, for example, reduced glucose uptake by astrocytes.…”

“…Marker of Enhanced Astrocyte S100B S100B is a calcium-binding protein, a biomarker of brain damage and stress that is synthesized by oligodendrocytes and astrocytes. It is also secreted by CD8T-lymphocytes and NK-cells during their stimulation, inducing microglial migration through increased cytokine expression (Michetti et al, 2019). The level of S100B was increased by almost two times compared to the healthy control groups, but its increase was observed in schizophrenia patients is not uniform (Aleksovska et al, 2014).…”

“…Adult astrocytes also express calcium-binding protein S100B, glutamate-aspartate transporter/ excitatory amino acid transporter 1 (EAAT1), and glutamate transporter (GLT-1) (Iglesias et al, 2017). Markers of enhanced astrocyte response are usually GFAP and S100B (Kim et al, 2018;Michetti et al, 2019).…”

Early predictors of perinatal brain damage: the role of neurobiomarkers

“…S100B has been detected in different biological fluids such as amniotic, CSF, blood, urine, saliva and milk [16][17][18][19][20][21][22][23]. It has neurotrophic effects at physiologic levels (nanomolar), but becomes neurotoxic at high concentrations (micromolar) [24][25][26][27].…”

Hyaluronic acid particle hydrogels decrease cerebral atrophy and promote pro-reparative astrocyte/axonal infiltration in the core after ischemic stroke

“…This data suggests that the astrocytes that are infiltrating the MAP gel are less reactive and potentially more pro-reparative. We also observe a significantly higher percentage of reactive astrocytes expressing S100b in the sham condition(~69%) compared to the 3.5% MAP gel (~26%), with high expression of S100b considered pathological 40,41 (Fig. 3E).…”