A Critical Analysis of the Role of the Neurotrophic Protein S100B in Acute Brain Injury

Department of Neurosurgery, Georg August University, Göttingen, Germany.
Journal of Neurotrauma (Impact Factor: 3.71). 09/2006; 23(8):1185-200. DOI: 10.1089/neu.2006.23.1185
Source: PubMed


We provide a critical analysis of the relevance of S100B in acute brain injury emphazising the beneficial effect of its biological properties. S100B is a calcium-binding protein, primarily produced by glial cells, and exerts auto- and paracrine functions. Numerous reports indicate, that S100B is released after brain insults and serum levels are positively correlated with the degree of injury and negatively correlated with outcome. However, new data suggest that the currently held view, that serum measurement of S100B is a valid "biomarker" of brain damage in traumatic brain injury (TBI), does not acknowlege the multifaceted release pattern and effect of the blood-brain barrier disruption upon S100B levels in serum. In fact, serum and brain S100B levels are poorly correlated, with serum levels dependent primarily on the integrity of the blood-brain barrier, and not the level of S100B in the brain. The time profile of S100B release following experimental TBI, both in vitro and in vivo, suggests a role of S100B in delayed reparative processes. Further, recent findings provide evidence, that S100B may decrease neuronal injury and/or contribute to repair following TBI. Hence, S100B, far from being a negative determinant of outcome, as suggested previously in the human TBI and ischemia literature, is of potential therapeutic value that could improve outcome in patients who sustain various forms of acute brain damage.

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Available from: Andrea Kleindienst, Dec 25, 2013
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    • "The increased level of S100β in the hippocampus of 81 day-old young rats exposed to LTG and TPM in utero (Fig. 3B1 and B2) appearantly results from upregulation of S100β expression in astrocytes [28], which is likely to be due to neurodegeneration induced by TPM and LTG in utero. It has been suggested that increments of S100β may improve neurogenesis, particularly in the hippocampus [29] and also stimulate glial proliferation and neuronal survival and protect neurons against glutamate excitotoxicity [30]. NCAM is capable of incorporating long chains of α 2,8 polysialic acid (PSA) [31]. "
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    ABSTRACT: Antiepileptic drugs (AED) which are used to treat seizures in pregnant women, infants, and young children may cause cognitive impairment or other uncertain injury. However, the precise mechanisms responsible for the negative effects of new AEDs like lamotrigine (LTG) and topiramate (TPM) in the developing brain are still unclear. To investigate the GFAP, NCAM and S100B levels in the whole brain of newborn rats on postnatal 1 day and in the hippocampus of adult rats to find out the effect of TPM and LTG on cognitive impairment and brain maturation. Twenty eight pregnant rats were randomly divided into 7 groups with 4 animals in each group. The first group, receiving no drugs, was assigned as the control group. The study groups received intraperitoneal TPM or LTG injections in each trimester. Western blot analysis of the GFAP, NCAM and S100B was performed in the offspring. Behavioral tests were performed at postnatal day 75. The rats in the TPM-I and TPM-III groups had a significant impairment in escape latency on the 5th day as compared to the control rats in a Morris water maze test. In addition, in the expression of astrocyte derived markers, GFAP was upregulated, whereas S100β and NCAM were downregulated in the whole brain on postnatal day 1, in offspring exposed to LTG and TPM in utero. The detrimental effects of TPM and LTG appear to be confined particularly to the early stages of brain development. And TPM seems to have a partial role in the cognitive impairment.
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    • "Furthermore , the crucial question of this field is still open: is it the damaged, decomposing astrocytes that release S100B to the circulation, or is this a result of an active release from intact astrocytes as an attempt to repair neuronal damage? Experts on the field tend to favor the protective role of S100B which is induced by a yet unknown degenerative mechanism involved in the pathogenesis of depression (Hetzel et al., 2005; Kleindienst and Ross Bullock, 2006; Steiner et al., 2006). The use of in vivo localized proton magnetic resonance spectroscopy (MRS) is another promising approach to identify potential biomarkers for neuropsychiatric disorders and it might be the right tool to identify glial specific biomarker(s) in the brain. "
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    • "In 2003, there was published a review of 18 clinical studies (involving 1085 patients) of the S100B protein as a marker of brain damage (Kleindienst & Ross Bullock, 2006). In 2004 and 2005, another 6 papers appeared (involving more than 600 adults) on the correlations between an elevated concentration of the S100B protein and poor outcome after brain injury (Kleindienst & Ross Bullock, 2006). The highest S100B protein serum level was observed just after an injury (Ingebrigtsen & Romner, 2003), then normalized within 24 hours, even in patients with poor outcome (Kleindienst & Ross Bullock, 2006). "

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