NSE and S100B belong among the so-called structural proteins of the central nervous system (CNS). Lately, this group of structural proteins has been profusely used as specific biomarkers of CNS tissue damage. So far, the majority of the research papers have focused predominantly on the concentrations of these proteins in blood in relation to CNS damage of various origins. Considering the close anatomic and functional relationship between the brain or spinal cord and cerebrospinal fluid (CSF), in case of a CNS injury, a rapid and pronounced increase of the concentrations of structural proteins specifically in CSF takes place. This study inquires into the physiological concentrations of NSE and S100B proteins in CSF, carried out on a sufficiently large group of 601 patients. The detected values can be used for determination of a normal reference range in CSF in a clinical laboratory diagnostics.

Laboratory for CSF and Neuroimmunology Topelex Ltd 190 00 Prague Czech Republic

Laboratory for CSF and Neuroimmunology Topelex Ltd 190 00 Prague Czech Republic ; Department of Biochemistry and Microbiology The Institute of Chemical Technology 166 28 Prague Czech Republic

Laboratory for CSF and Neuroimmunology Topelex Ltd 190 00 Prague Czech Republic ; Department of Biology and Medical Genetics Charles University 2nd Faculty of Medicine and University Hospital Motol 150 06 Prague Czech Republic

Laboratory for CSF and Neuroimmunology Topelex Ltd 190 00 Prague Czech Republic ; Department of Neurology The Military University Hospital Prague 169 02 Prague Czech Republic

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Michetti F., Massaro A., Russo G., Rigon G. The S-100 antigen in cerebrospinal fluid as a possible index of cell injury in the nervous system. Journal of the Neurological Sciences. 1980;44(2-3):259–263. doi: 10.1016/0022-510X(80)90133-1. PubMed DOI

Schäfer B. W., Heizmann C. W. The S100 family of EF-hand calcium-binding proteins: functions and pathology. Trends in Biochemical Sciences. 1996;21(4):134–140. doi: 10.1016/0968-0004(96)10020-7. PubMed DOI

Zhu L., Okano S., Takahara M., et al. Expression of S100 protein family members in normal skin and sweat gland tumors. Journal of Dermatological Science. 2013;70(3):211–219. doi: 10.1016/j.jdermsci.2013.03.002. PubMed DOI

Michetti F., Gazzolo D. Perinatal S100B protein assessment in human unconventional biological fluids: a minireview and new perspectives. Cardiovascular Psychiatry and Neurology. 2010;2010:5. doi: 10.1155/2010/703563.703563 PubMed DOI PMC

Donato R., Sorci G., Riuzzi F., et al. S100B's double life: intracellular regulator and extracellular signal. Biochimica et Biophysica Acta—Molecular Cell Research. 2009;1793(6):1008–1022. doi: 10.1016/j.bbamcr.2008.11.009. PubMed DOI

Rainey T., Lesko M., Sacho R., Lecky F., Childs C. Predicting outcome after severe traumatic brain injury using the serum S100B biomarker: results using a single (24 h) time-point. Resuscitation. 2009;80(3):341–345. doi: 10.1016/j.resuscitation.2008.11.021. PubMed DOI

Foell D., Wittkowski H., Vogl T., Roth J. S100 proteins expressed in phagocytes: a novel group of damage-associated molecular pattern molecules. Journal of Leukocyte Biology. 2007;81(1):28–37. doi: 10.1189/jlb.0306170. PubMed DOI

Guerra M. C., Tortorelli L. S., Galland F., et al. Lipopolysaccharide modulates astrocytic S100B secretion: a study in cerebrospinal fluid and astrocyte cultures from rats. Journal of Neuroinflammation. 2011;8, article 128 doi: 10.1186/1742-2094-8-128. PubMed DOI PMC

Sorci G., Bianchi R., Riuzzi F., et al. S100B protein, a damage-associated molecular pattern protein in the brain and heart, and beyond. Cardiovascular Psychiatry and Neurology. 2010;2010:13. doi: 10.1155/2010/656481.65648 PubMed DOI PMC

Michetti F., Corvino V., Geloso M. C., et al. The S100B protein in biological fluids: more than a lifelong biomarker of brain distress. Journal of Neurochemistry. 2012;120(5):644–659. doi: 10.1111/j.1471-4159.2011.07612.x. PubMed DOI

Sen J., Belli A. S100B in neuropathologic states: the CRP of the brain? Journal of Neuroscience Research. 2007;85(7):1373–1380. doi: 10.1002/jnr.21211. PubMed DOI

Rider C. C., Taylor C. B. Enolase isoenzymes. II. Hybridization studies, developmental and phylogenetic aspects. Biochimica et Biophysica Acta. 1975;405(1):175–187. doi: 10.1016/0005-2795(75)90328-1. PubMed DOI

Ondrkalová M., Kalnovičová T., Štofko J., Traubner P., Turčáni P. Levels of neuron-specific anolase in focal brain ischaemia. Klinicka Biochemie a Metabolismus. 2006;14(4):202–206.

Planche V., Brochet C., Bakkouch A., Bernard M. Importance of hemolysis on neuron-specific enolase measurement. Annales de Biologie Clinique. 2010;68(2):239–242. doi: 10.1684/abc.2010.0422. PubMed DOI

Persson L., Hardemark H.-G., Gustafsson J., et al. S-100 protein and neuron-specific enolase in cerebrospinal fluid and serum: Markers of cell damage in human central nervous system. Stroke. 1987;18(5):911–918. doi: 10.1161/01.STR.18.5.911. PubMed DOI

Kleine T. O., Benes L., Zöfel P. Studies of the brain specificity of S100B and neuron-specific enolase (NSE) in blood serum of acute care patients. Brain Research Bulletin. 2003;61(3):265–279. doi: 10.1016/S0361-9230(03)00090-X. PubMed DOI

Zetterberg H., Smith D. H., Blennow K. Biomarkers of mild traumatic brain injury in cerebrospinal fluid and blood. Nature Reviews Neurology. 2013;9(4):201–210. doi: 10.1038/nrneurol.2013.9. PubMed DOI PMC

Calderon L. M., Guyette F. X., Doshi A. A., Callaway C. W., Rittenberger J. C. Combining NSE and S100B with clinical examination findings to predict survival after resuscitation from cardiac arrest. Resuscitation. 2014;85:1025–1029. doi: 10.1016/j.resuscitation.2014.04.020. PubMed DOI PMC

Ingebrigtsen T., Romner B., Marup-Jensen S., et al. The clinical value of serum S-100 protein measurements in minor head injury: a Scandinavian multicentre study. Brain Injury. 2000;14(12):1047–1055. doi: 10.1080/02699050050203540. PubMed DOI

Biberthaler P., Mussack T., Wiedemann E., et al. Rapid identification of high-risk patients after minor head trauma (MHT) by assessment of S-100B: ascertainment of a cut-off level. European Journal of Medical Research. 2002;7(4):164–170. PubMed

Berger R. P., Pierce M. C., Wisniewski S. R., et al. Neuron-specific enolase and S100B in cerebrospinal fluid after severe traumatic brain injury in infants and children. Pediatrics. 2002;109(2):p. E31. doi: 10.1542/peds.109.2.e31. PubMed DOI

Hayakata T., Shiozaki T., Tasaki O., et al. Changes in CSF S100B and cytokine concentrations in early-phase severe traumatic brain injury. Shock. 2004;22(2):102–107. doi: 10.1097/01.shk.0000131193.80038.f1. PubMed DOI

Kochanek P. M., Berger R. P., Bayir H., Wagner A. K., Jenkins L. W., Clark R. S. B. Biomarkers of primary and evolving damage in traumatic and ischemic brain injury: diagnosis, prognosis, probing mechanisms, and therapeutic decision making. Current Opinion in Critical Care. 2008;14(2):135–141. doi: 10.1097/MCC.0b013e3282f57564. PubMed DOI

Büttner T., Weyers S., Postert T., Sprengelmeyer R., Kuhn W. S-100 protein: serum marker of focal brain damage after ischemic territorial MCA infarction. Stroke. 1997;28(10):1961–1965. doi: 10.1161/01.STR.28.10.1961. PubMed DOI

Petzold A., Michel P., Stock M., Schluep M. Glial and axonal body fluid biomarkers are related to infarct volume, severity, and outcome. Journal of Stroke and Cerebrovascular Diseases. 2008;17(4):196–203. doi: 10.1016/j.jstrokecerebrovasdis.2008.02.002. PubMed DOI

Herrmann M., Vos P., Wunderlich M. T., de Bruijn C. H. M. M., Lamers K. J. B. Release of glial tissue-specific proteins after acute stroke. Stroke. 2000;31(11):2670–2677. doi: 10.1161/01.STR.31.11.2670. PubMed DOI

Foerch C., Singer O. C., Neumann-Haefelin T., Du Mesnil de Rochemont R., Steinmetz H., Sitzer M. Evaluation of serum S100B as a surrogate marker for long-term outcome and infarct volume in acute middle cerebral artery infarction. Archives of Neurology. 2005;62(7):1130–1134. doi: 10.1001/archneur.62.7.1130. PubMed DOI

Brouns R., de Vil B., Cras P., de Surgeloose D., Mariën P., de Deyn P. P. Neurobiochemical markers of brain damage in cerebrospinal fluid of acute ischemic stroke patients. Clinical Chemistry. 2010;56(3):451–458. doi: 10.1373/clinchem.2009.134122. PubMed DOI

Huang M., Dong X.-Q., Hu Y.-Y., Yu W.-H., Zhang Z.-Y. High S100B levels in cerebrospinal fluid and peripheral blood of patients with acute basal ganglial hemorrhage are associated with poor outcome. World Journal of Emergency Surgery. 2010;1(1) PubMed PMC

Jung C. S., Lange B., Zimmermann M., Seifert V. CSF and serum biomarkers focusing on cerebral vasospasm and ischemia after subarachnoid hemorrhage. Stroke Research and Treatment. 2013;2013:7. doi: 10.1155/2013/560305.560305 PubMed DOI PMC

Moritz S., Warnat J., Bele S., Graf B. M., Woertgen C. The prognostic value of NSE and S100B from serum and cerebrospinal fluid in patients with spontaneous subarachnoid hemorrhage. Journal of Neurosurgical Anesthesiology. 2010;22(1):21–31. doi: 10.1097/ANA.0b013e3181bdf50d. PubMed DOI

Johnsson P., Bäckström M., Bergh C., Jönsson H., Lührs C., Alling C. Increased S100B in blood after cardiac surgery is a powerful predictor of late mortality. The Annals of Thoracic Surgery. 2003;75(1):162–168. doi: 10.1016/S0003-4975(02)04318-7. PubMed DOI

Georgiadis D., Berger A., Kowatschev E., et al. Predictive value of S-100β and neuron-specific enolase serum levels for adverse neurologic outcome after cardiac surgery. The Journal of Thoracic and Cardiovascular Surgery. 2000;119(1):138–147. PubMed

de Vries J., Thijssen W. A. M. H., Snels S. E. A., Menovsky T., Peer N. G. M., Lamers K. J. B. Intraoperative values of S-100 protein, myelin basic protein, lactate, and albumin in the CSF and serum of neurosurgical patients. Journal of Neurology, Neurosurgery & Psychiatry. 2001;71(5):671–674. doi: 10.1136/jnnp.71.5.671. PubMed DOI PMC

Mattusch C., Diederich K.-W., Schmidt A., et al. Effect of carotid artery stenting on the release of S-100B and neurone-specific enolase. Angiology. 2011;62(5):376–380. doi: 10.1177/0003319710387920. PubMed DOI

Seregni E., Massaron S., Martinetti A., et al. S100 protein serum levels in cutaneous malignant melanoma. Oncology Reports. 1998;5(3):601–604. PubMed

Harding M., McAllister J., Hulks G., et al. Neurone specific enolase (NSE) in small cell lung cancer: a tumour marker of prognostic significance? British Journal of Cancer. 1990;61(4):605–607. doi: 10.1038/bjc.1990.134. PubMed DOI PMC

Green A. J. E., Thompson E. J., Stewart G. E., et al. Use of 14−3−3 and other brain-specific proteins in CSF in the diagnosis of variant Creutzfeldt-Jakob disease. Journal of Neurology, Neurosurgery & Psychiatry. 2001;70(6):744–748. doi: 10.1136/jnnp.70.6.744. PubMed DOI PMC

Nygaard Ø., Langbakk B., Romner B. Age- and sex-related changes of S-100 protein concentrations in cerebrospinal fluid and serum in patients with no previous history of neurological disorder. Clinical Chemistry. 1997;43(3):541–543. PubMed

Kelbich P., Hejčl A., Krulichová I. S., et al. Coefficient of energy balance, a new parameter for basic investigation of the cerebrospinal fluid. Clinical Chemistry and Laboratory Medicine. 2014;52(7):1009–1017. doi: 10.1515/cclm-2013-0953. PubMed DOI

Bořecká K., Adam P., Sobek O., Hajduková L., Lánská V., Nekola P. Coefficient of energy balance: effective tool for early differential diagnosis of CNS diseases. BioMed Research International. 2013;2013:8. doi: 10.1155/2013/745943.745943 PubMed DOI PMC

Bonfrer J. M. G., Korse C. M., Nieweg O. E., Rankin E. M. The luminescence immunoassay S-100: a sensitive test to measure circulating S-100B: its prognostic value in malignant melanoma. British Journal of Cancer. 1998;77(12):2210–2214. doi: 10.1038/bjc.1998.368. PubMed DOI PMC

Gazzolo D., Michetti F., Bruschettini M., et al. Pediatric concentrations of S100B protein in blood: age- and sex-related changes. Clinical Chemistry. 2003;49(6):967–970. doi: 10.1373/49.6.967. PubMed DOI

van Engelen B. G. M., Lamers K. J. B., Gabreels F. J. M., Wevers R. A., van Geel W. J. A., Borm G. F. Age-related changes of neuron-specific enolase, S-100 protein, and myelin basic protein concentrations in cerebrospinal fluid. Clinical Chemistry. 1992;38(6):813–816. PubMed

Reiber H. Dynamics of brain-derived proteins in cerebrospinal fluid. Clinica Chimica Acta. 2001;310(2):173–186. doi: 10.1016/S0009-8981(01)00573-3. PubMed DOI

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