The S100B is a calcium-binding peptide and is used as a parameter of glial activation and/or death in many disorders of the central nervous system (CNS). It plays important roles in normal CNS development and recovery after injury. Although S100B is mainly found in astroglial and Schwann cells, it also has extracerebral sources. S100B is a useful neurobiochemical marker of brain damage such as in circulatory arrest, stroke and traumatic brain injury. S100B is also associated with neurodegenerative diseases like Alzheimer's disease or other chronic neurological diseases. S100B is a calcium-binding protein produced mainly by astrocytes. Astrocytes are a subtype of glial cells that make up the majority of cells in the human central nervous system (CNS). They perform metabolic, structural, homeostatic, and neuroprotective tasks such as clearing excess neurotransmitters, stabilizing and regulating the blood-brain barrier, and promoting synapse formation.
S100B is a reporter of blood-brain barrier (BBB) integrity which appears in blood when the BBB is breached. Circulating S100B derives from either extracranial sources or release into circulation by normal fluctuations in BBB integrity or pathologic BBB disruption (BBBD). It is also expressed in the Schwann cells of the peripheral nervous system, and outside the nervous system in melanocytes, adipocytes and chondrocytes. This protein is localized in the cytoplasm and nucleus of a wide range of cells and involved in the regulation of several cellular processes such as cell cycle progression and differentiation. Studies have shown extravasated S100B may trigger a pathologic autoimmune reaction linking systemic and CNS immune responses.
What is the blood brain barrier?
Blood brain barrier (BBB) is a term used to describe the microvasculature structures and function of the central nervous system (CNS); these properties tightly regulate the movement of molecules, ions, and cells between the blood and CNS.
In layman’s terms, the BBB only lets in what is needed and keeps out what is harmful.
The BBB is critical for protecting the CNS from toxins, pathogens, inflammation, injury, and disease. Dysfunction of the BBB can lead to neuronal dysfunction and degeneration.
The BBB plays a central role in healing and recovery after head injuries, for instance. A recent finding due to medical focus on amateur and professional athletes is that concussion patients often develop chronic health conditions after their head injury.
Within 20 minutes of a head injury, the intestinal barrier and blood brain barrier open up and become permeable (“leaky”) due to shock and physiological stress. A permeable blood brain barrier and a permeable gut barrier cause inflammation, which then causes the autonomic nervous system to become very reactive to things it normally would not be.
If not treated, a permeable gut and a permeable brain may lead to lifelong ailments that negatively and progressively affect health.
Additional notes:
- Serum S100B and S100B autoantibody levels may help to identify which lung cancer patients have brain metastases.
- High levels of extracellular S100B have been detected under various clinical conditions, for example, brain trauma, ischemia and neurodegenerative, and inflammatory and psychiatric diseases. A recent study showed that S100B levels were higher in serum from fibromyalgia patients with lower pressure pain thresholds.
- Elevated levels of the astroglial protein S100B have been shown to predict sport-related concussion. However, S100B levels within an athlete can vary depending on the type of physical activity (PA) engaged in and the methodologic approach used to measure them. Thus, appropriate reference values in the diagnosis of concussed athletes remain undefined.
- S100B antibodies have primary associations with concussions and traumatic brain injury (TBI). Antibodies develop early– before the development of gross changes, making it a target antibody for prevention.
References:
Bargerstock E, Puvenna V, Iffland P, Falcone T, Hossain M, Vetter S, Man S, Dickstein L, Marchi N, Ghosh C, Carvalho-Tavares J, Janigro D. Is peripheral immunity regulated by blood-brain barrier permeability changes? PLoS One. 2014 Jul 2;9(7):e101477. doi: 10.1371/journal.pone.0101477. PMID: 24988410; PMCID: PMC4079719.
Poletaev AB, Morozov SG, Gnedenko BB, Zlunikin VM, Korzhenevskey DA. Serum anti-S100b, anti-GFAP and anti-NGF autoantibodies of IgG class in healthy persons and patients with mental and neurological disorders. Autoimmunity. 2000;32(1):33-8. doi: 10.3109/08916930008995985. PMID: 10958173.
Choi H, Puvenna V, Brennan C, Mahmoud S, Wang XF, Phillips M, Janigro D, Mazzone P. S100B and S100B autoantibody as biomarkers for early detection of brain metastases in lung cancer. Transl Lung Cancer Res. 2016 Aug;5(4):413-9. doi: 10.21037/tlcr.2016.07.08. PMID: 27652205; PMCID: PMC5009084.
Yardan T, Erenler AK, Baydin A, Aydin K, Cokluk C. Usefulness of S100B protein in neurological disorders. J Pak Med Assoc. 2011 Mar;61(3):276-81. PMID: 21465945.
Cristóvão JS, Gomes CM. S100 Proteins in Alzheimer's Disease. Front Neurosci. 2019 May 16;13:463. doi: 10.3389/fnins.2019.00463. PMID: 31156365; PMCID: PMC6532343.
Role of Extracellular Damage-Associated Molecular Pattern Molecules (DAMPs) as Mediators of Persistent Pain (Chapter Nine) Jungo Kato, Camilla I. Svensson, Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden
Ravichandran Ramasamy, Susan J. Vannucci, Shirley Shi Du Yan, Kevan Herold, Shi Fang Yan, Ann Marie Schmidt, Advanced glycation end products and RAGE: a common thread in aging, diabetes, neurodegeneration, and inflammation, Glycobiology, Volume 15, Issue 7, July 2005, Pages 16R–28R, https://doi.org/10.1093/glycob/cwi053
Schulte S, Podlog LW, Hamson-Utley JJ, Strathmann FG, Strüder HK. A systematic review of the biomarker S100B: implications for sport-related concussion management. J Athl Train. 2014 Nov-Dec;49(6):830-50. doi: 10.4085/1062-6050-49.3.33. PMID: 25299445; PMCID: PMC4264656.
Links:
https://www.ncbi.nlm.nih.gov/books/NBK545142/#:~:text=Astrocytes%20are%20a%20subtype%20of,barrier%2C%20and%20promoting%20synapse%20formation.
Anti-s100b (IgG + IgA)
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