S100B in brain damage and neurodegeneration

Abstract

S100B is a calcium-binding peptide produced mainly by astrocytes that exert paracrine and autocrine effects on neurons and glia. Some knowledge has been acquired from in vitro and in vivo animal experiments to understand S100B's roles in cellular energy metabolism, cytoskeleton modification, cell proliferation, and differentiation. Also, insights have been gained regarding the interaction between S100B and the cerebral immune system, and the regulation of S100B activity through serotonergic transmission. Secreted glial S100B exerts trophic or toxic effects depending on its concentration. At nanomolar concentrations, S100B stimulates neurite outgrowth and enhances survival of neurons during development. In contrast, micromolar levels of extracellular S100B in vitro stimulate the expression of proinflammatory cytokines and induce apoptosis. In animal studies, changes in the cerebral concentration of S100B cause behavioral disturbances and cognitive deficits. In humans, increased S100B has been detected with various clinical conditions. Brain trauma and ischemia is associated with increased S100B concentrations, probably due to the destruction of astrocytes. In neurodegenerative, inflammatory and psychiatric diseases, increased S100B levels may be caused by secreted S100B or release from damaged astrocytes. This review summarizes published findings on S100B regarding human brain damage and neurodegeneration. Findings from in vitro and in vivo animal experiments relevant for human neurodegenerative diseases and brain damage are reviewed together with the results of studies on traumatic, ischemic, and inflammatory brain damage as well as neurodegenerative and psychiatric disorders. Methodological problems are discussed and perspectives for future research are outlined.

S100B Serum Levels and Long-Term Improvement of Negative Symptoms in Patients with Schizophrenia

“…Even though the S100B serum concentrations in schizophrenic patients were significantly increased compared to healthy controls the absolute values were within a range that has been considered normal in studies designed to discover brain damage (for a review see, Rothermundt et al, 2003). In brain damage, S100B levels are measured to detect a vast destruction of astrocytes.…”

“…Since a healthy brain requires the potential to implement proliferative as well as differentiating mechanisms according to varying requirements, S100B should be present in balanced amounts (Donato, 2001;Rothermundt et al, 2003). We still do not know what causes the loss of dendrites and synapses in brains of schizophrenic patients (Harrison, 1999;Powers, 1999;Selemon and Goldman-Rakic, 1999;McGlashan and Hoffman, 2000), but from our knowledge concerning the mechanisms of regeneration and degeneration it appears likely that S100B might be involved in this process (Donato, 2001;Rothermundt et al, 2003). The increased S100B concentrations in patients with schizophrenia might cause a shift in the regeneration-degeneration balance towards degeneration so that a rarification of synapses and dendrites might result.…”

“…Physiologically or pathologically (ie excessively) released S100B reaches the extracellular compartment and cerebrospinal fluid before entering the bloodstream (Beaudeux et al, 1999). In animal studies, changes in the cerebral concentration of S100B cause behavioral disturbances and cognitive deficits (for a review see, Donato, 2001;Heizmann et al, 2002;Rothermundt et al, 2003Rothermundt et al, , 2004.…”

A Novel Microwave Sensor to Detect Specific Biomarkers in Human Cerebrospinal Fluid and Their Relationship to Cellular Ischemia During Thoracoabdominal Aortic Aneurysm Repair

“…However, although there is a good correlation to spinal cord ischaemia and rises in CSF lactate, there is a lag between its rise and development of CSF lactate [25]. There is now considerable interest with respects to specific biomarkers that can be biochemically analysed and are more sensitive to spinal cord ischaemia than lactate [26][27][28][29][30][31]. In particular, interest has arisen in the area of protein level monitoring, and so the aim of this work is to determine the ability of EM wave sensors to measure varying quantities of protein.…”

Serum Levels of Biochemical Markers of Traumatic Brain Injury

“…The S-100β assay used in this investigation has a detection limit of 10 pg/mL, which is lower than that for other commercially available S-100β assays [26]; furthermore, the 98th percentile reference limit for this assay in a healthy adult control population is 21 pg/mL [17], whereas other commercial assays have normal reference limits exceeding 100 pg/mL [27]. Apparent differences in assay specificities for the brain-specific isoform of the S-100 protein would account for the fact that the serum S-100β levels observed in the current investigation are generally lower than those reported in previous studies of S-100β in TBI [26].…”