Skip to main content
Erschienen in: Child's Nervous System 8/2015

01.08.2015 | Original Paper

Increased cerebrospinal fluid cleaved tau protein (C-tau) levels suggest axonal damage in pediatric patients with brain tumors

verfasst von: Pelin Cengiz, Frank Zemlan, Jens C. Eickhoff, Richard Ellenbogen, Jerry J. Zimmerman

Erschienen in: Child's Nervous System | Ausgabe 8/2015

Einloggen, um Zugang zu erhalten

Abstract

Objective

This study aims to determine if cerebrospinal fluid/serum cleaved tau protein and CSF 9-hydroxyoctadecadienoic acid levels, reflecting potential biomarkers of overall neuronal injury and lipid peroxidation, respectively, are elevated in brain tumor patients compared with controls.

Design

This article is a prospective clinical observational study.

Setting

This study is conducted at a tertiary-care children’s hospital.

Patients

Our participants are children younger than or equal to 18 years of age undergoing brain tumor surgery.

Measurements and main results

During the study period, 26 consecutive patients newly diagnosed with brain tumors who met the inclusion criteria were prospectively enrolled. Baseline cerebrospinal fluid analysis of cleaved tau and 9-hydroxyoctadecadienoic acid were measured in 15 patients. Cerebrospinal fluid cleaved tau and 9-hydroxyoctadecadienoic acid levels were measured in 22 patients for post-surgery days 1 and 3. Serum cleaved tau levels were measured for 20 and 18 patients for post-surgery days 1 and 3, respectively. The presence of a brain tumor significantly increased the baseline cerebrospinal fluid cleaved tau levels but did not affect cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels. Similarly, there was a significant increase in post-surgery day 1 cerebrospinal fluid cleaved tau levels from baseline (p = 0.01) and a trend toward significant decrease in post-surgery day 3 cerebrospinal fluid cleaved tau from day 1 (p = 0.07). 9-Hydroxyoctadecadienoic acid concentrations remained relatively constant over time with no differences noted between the control and brain tumor patients. There was a trend towards a significant association between cerebrospinal fluid cleaved tau levels and duration of symptoms (p = 0.07).

Conclusions

Cerebrospinal fluid cleaved tau levels in children with newly diagnosed brain tumors exhibit markedly elevated cerebrospinal fluid cleaved tau levels, suggesting axonal damage. This axonal injury does not seem to correlate with lipid peroxidation at least when as assessed by cerebrospinal fluid 9-hydroxyoctadecadienoic acid levels. There was no association found between the biomarkers and multiple independent variables obtained at pre- and post-tumor resection.
Literatur
1.
Zurück zum Zitat Gurney JG (1999) Topical topics: brain cancer incidence in children: time to look beyond the trends. Med Pediatr Oncol 33(2):110–112PubMedCrossRef Gurney JG (1999) Topical topics: brain cancer incidence in children: time to look beyond the trends. Med Pediatr Oncol 33(2):110–112PubMedCrossRef
2.
Zurück zum Zitat Rosemberg S, Fujiwara D (2005) Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 21(11):940–944CrossRef Rosemberg S, Fujiwara D (2005) Epidemiology of pediatric tumors of the nervous system according to the WHO 2000 classification: a report of 1,195 cases from a single institution. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 21(11):940–944CrossRef
3.
Zurück zum Zitat Bleyer WA (1999) Epidemiologic impact of children with brain tumors. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 15(11–12):758–763CrossRef Bleyer WA (1999) Epidemiologic impact of children with brain tumors. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 15(11–12):758–763CrossRef
4.
Zurück zum Zitat Grill J et al (2008) Childhood cerebral tumors: morbidity and follow-up into adulthood. Neuro-Chirurgie 54(5):623–641PubMedCrossRef Grill J et al (2008) Childhood cerebral tumors: morbidity and follow-up into adulthood. Neuro-Chirurgie 54(5):623–641PubMedCrossRef
5.
Zurück zum Zitat Vinchon M et al (2011) Radiation-induced tumors in children irradiated for brain tumor: a longitudinal study. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 27(3):445–453CrossRef Vinchon M et al (2011) Radiation-induced tumors in children irradiated for brain tumor: a longitudinal study. Child’s Nerv Syst: ChNS: Off J Int Soc Pediatr Neurosurg 27(3):445–453CrossRef
6.
Zurück zum Zitat Kochanek PM et al (2013) The potential for bio-mediators and biomarkers in pediatric traumatic brain injury and neurocritical care. Front Neurol 4:40PubMedCentralPubMedCrossRef Kochanek PM et al (2013) The potential for bio-mediators and biomarkers in pediatric traumatic brain injury and neurocritical care. Front Neurol 4:40PubMedCentralPubMedCrossRef
7.
8.
Zurück zum Zitat Kosik KS, Finch EA (1987) MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: an immunocytochemical study of cultured rat cerebrum. J Neurosci Off J Soc Neurosci 7(10):3142–3153 Kosik KS, Finch EA (1987) MAP2 and tau segregate into dendritic and axonal domains after the elaboration of morphologically distinct neurites: an immunocytochemical study of cultured rat cerebrum. J Neurosci Off J Soc Neurosci 7(10):3142–3153
9.
Zurück zum Zitat Zemlan FP et al (1999) Quantification of axonal damage in traumatic brain injury: affinity purification and characterization of cerebrospinal fluid tau proteins. J Neurochem 72(2):741–750PubMedCrossRef Zemlan FP et al (1999) Quantification of axonal damage in traumatic brain injury: affinity purification and characterization of cerebrospinal fluid tau proteins. J Neurochem 72(2):741–750PubMedCrossRef
10.
Zurück zum Zitat Zemlan FP, Mulchahey JJ, Gudelsky GA (2003) Quantification and localization of kainic acid-induced neurotoxicity employing a new biomarker of cell death: cleaved microtubule-associated protein-tau (C-tau). Neuroscience 121(2):399–409PubMedCrossRef Zemlan FP, Mulchahey JJ, Gudelsky GA (2003) Quantification and localization of kainic acid-induced neurotoxicity employing a new biomarker of cell death: cleaved microtubule-associated protein-tau (C-tau). Neuroscience 121(2):399–409PubMedCrossRef
11.
Zurück zum Zitat Irazuzta JE et al (2001) Serum cleaved tau protein and neurobehavioral battery of tests as markers of brain injury in experimental bacterial meningitis. Brain Res 913(1):95–105PubMedCrossRef Irazuzta JE et al (2001) Serum cleaved tau protein and neurobehavioral battery of tests as markers of brain injury in experimental bacterial meningitis. Brain Res 913(1):95–105PubMedCrossRef
12.
Zurück zum Zitat Irazuzta JE et al (2000) Hypothermia as an adjunctive treatment for severe bacterial meningitis. Brain Res 881(1):88–97PubMedCrossRef Irazuzta JE et al (2000) Hypothermia as an adjunctive treatment for severe bacterial meningitis. Brain Res 881(1):88–97PubMedCrossRef
13.
Zurück zum Zitat Irazuzta JE et al (2002) Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 30(11):2553–2559PubMedCrossRef Irazuzta JE et al (2002) Modulation of nuclear factor-kappaB activation and decreased markers of neurological injury associated with hypothermic therapy in experimental bacterial meningitis. Crit Care Med 30(11):2553–2559PubMedCrossRef
14.
Zurück zum Zitat Shaw GJ, Jauch EC, Zemlan FP (2002) Serum cleaved tau protein levels and clinical outcome in adult patients with closed head injury. Ann Emerg Med 39(3):254–257PubMedCrossRef Shaw GJ, Jauch EC, Zemlan FP (2002) Serum cleaved tau protein levels and clinical outcome in adult patients with closed head injury. Ann Emerg Med 39(3):254–257PubMedCrossRef
15.
Zurück zum Zitat Straiko MM et al (2006) Treatment with trimethyltin promotes the formation of cleaved tau in the rat brain. J Neurosci Res 84(5):1116–1123PubMedCrossRef Straiko MM et al (2006) Treatment with trimethyltin promotes the formation of cleaved tau in the rat brain. J Neurosci Res 84(5):1116–1123PubMedCrossRef
16.
Zurück zum Zitat Cengiz P et al (2008) Cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid concentrations in pediatric patients with hydrocephalus. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc 9(5):524–529 Cengiz P et al (2008) Cerebrospinal fluid cleaved-tau protein and 9-hydroxyoctadecadienoic acid concentrations in pediatric patients with hydrocephalus. Pediatr Crit Care Med J Soc Crit Care Med World Fed Pediatr Intensive Crit Care Soc 9(5):524–529
17.
Zurück zum Zitat Stoll LL, Morland MR, Spector AA (1994) 13-HODE increases intracellular calcium in vascular smooth muscle cells. Am J Physiol 266(4 Pt 1):C990–C996PubMed Stoll LL, Morland MR, Spector AA (1994) 13-HODE increases intracellular calcium in vascular smooth muscle cells. Am J Physiol 266(4 Pt 1):C990–C996PubMed
18.
Zurück zum Zitat Camacho M et al (1995) Interleukin-1 enhances the ability of cultured human umbilical vein endothelial cells to oxidize linoleic acid. J Biol Chem 270(29):17279–17286PubMedCrossRef Camacho M et al (1995) Interleukin-1 enhances the ability of cultured human umbilical vein endothelial cells to oxidize linoleic acid. J Biol Chem 270(29):17279–17286PubMedCrossRef
19.
Zurück zum Zitat Dandona P et al (2001) The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation. J Clin Endocrinol Metab 86(1):355–362PubMed Dandona P et al (2001) The suppressive effect of dietary restriction and weight loss in the obese on the generation of reactive oxygen species by leukocytes, lipid peroxidation, and protein carbonylation. J Clin Endocrinol Metab 86(1):355–362PubMed
20.
Zurück zum Zitat Henricks PA et al (1991) 9- and 13-hydroxy-linoleic acid possess chemotactic activity for bovine and human polymorphonuclear leukocytes. Prostaglandins 41(1):21–27PubMedCrossRef Henricks PA et al (1991) 9- and 13-hydroxy-linoleic acid possess chemotactic activity for bovine and human polymorphonuclear leukocytes. Prostaglandins 41(1):21–27PubMedCrossRef
21.
Zurück zum Zitat Ku G et al (1992) Induction of interleukin 1 beta expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid. J Biol Chem 267(20):14183–14188PubMed Ku G et al (1992) Induction of interleukin 1 beta expression from human peripheral blood monocyte-derived macrophages by 9-hydroxyoctadecadienoic acid. J Biol Chem 267(20):14183–14188PubMed
22.
Zurück zum Zitat Tontonoz P et al (1998) PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93(2):241–252PubMedCrossRef Tontonoz P et al (1998) PPARgamma promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93(2):241–252PubMedCrossRef
23.
Zurück zum Zitat Fischer B, von Knethen A, Brune B (2002) Dualism of oxidized lipoproteins in provoking and attenuating the oxidative burst in macrophages: role of peroxisome proliferator-activated receptor-gamma. J Immunol 168(6):2828–2834PubMedCrossRef Fischer B, von Knethen A, Brune B (2002) Dualism of oxidized lipoproteins in provoking and attenuating the oxidative burst in macrophages: role of peroxisome proliferator-activated receptor-gamma. J Immunol 168(6):2828–2834PubMedCrossRef
24.
Zurück zum Zitat Li WG et al (2003) Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity. Free Radic Biol Med 34(7):937–946PubMedCrossRef Li WG et al (2003) Activation of NAD(P)H oxidase by lipid hydroperoxides: mechanism of oxidant-mediated smooth muscle cytotoxicity. Free Radic Biol Med 34(7):937–946PubMedCrossRef
25.
Zurück zum Zitat Inouye M, Mio T, Sumino K (1999) Formation of 9-hydroxy linoleic acid as a product of phospholipid peroxidation in diabetic erythrocyte membranes. Biochim Biophys Acta 1438(2):204–212PubMedCrossRef Inouye M, Mio T, Sumino K (1999) Formation of 9-hydroxy linoleic acid as a product of phospholipid peroxidation in diabetic erythrocyte membranes. Biochim Biophys Acta 1438(2):204–212PubMedCrossRef
26.
Zurück zum Zitat Metzger K et al (1995) Lipoxygenase products in human saliva: patients with oral cancer compared to controls. Free Radic Biol Med 18(2):185–194PubMedCrossRef Metzger K et al (1995) Lipoxygenase products in human saliva: patients with oral cancer compared to controls. Free Radic Biol Med 18(2):185–194PubMedCrossRef
27.
Zurück zum Zitat Kreil P et al (1998) Strong increase of 9-hydroxy-10,12-octadecadienoic acid in low density lipoprotein after a hemorrhagic shock. Zeitschrift fur Naturforschung C, J Biosci 53(9–10):876–882 Kreil P et al (1998) Strong increase of 9-hydroxy-10,12-octadecadienoic acid in low density lipoprotein after a hemorrhagic shock. Zeitschrift fur Naturforschung C, J Biosci 53(9–10):876–882
28.
Zurück zum Zitat Cobbs CS et al (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55(4):727–730PubMed Cobbs CS et al (1995) Expression of nitric oxide synthase in human central nervous system tumors. Cancer Res 55(4):727–730PubMed
29.
Zurück zum Zitat Spindler SA et al (1996) Significance and immunoassay of 9- and 13-hydroxyoctadecadienoic acids. Biochem Biophys Res Commun 218(1):187–191PubMedCrossRef Spindler SA et al (1996) Significance and immunoassay of 9- and 13-hydroxyoctadecadienoic acids. Biochem Biophys Res Commun 218(1):187–191PubMedCrossRef
30.
Zurück zum Zitat de Bont JM et al (2008) Increased total-tau levels in cerebrospinal fluid of pediatric hydrocephalus and brain tumor patients. Eur J Paediatr Neurol 12(4):334–341PubMedCrossRef de Bont JM et al (2008) Increased total-tau levels in cerebrospinal fluid of pediatric hydrocephalus and brain tumor patients. Eur J Paediatr Neurol 12(4):334–341PubMedCrossRef
31.
Zurück zum Zitat Trojanowski JQ et al (1989) Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem 37(2):209–215PubMedCrossRef Trojanowski JQ et al (1989) Distribution of tau proteins in the normal human central and peripheral nervous system. J Histochem Cytochem 37(2):209–215PubMedCrossRef
32.
Zurück zum Zitat Sivanandam TM, Thakur MK (2012) Traumatic brain injury: a risk factor for Alzheimer’s disease. Neurosci Biobehav Rev 36(5):1376–1381PubMedCrossRef Sivanandam TM, Thakur MK (2012) Traumatic brain injury: a risk factor for Alzheimer’s disease. Neurosci Biobehav Rev 36(5):1376–1381PubMedCrossRef
33.
Zurück zum Zitat Tsitsopoulos PP, Marklund N (2013) Amyloid-beta peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: a review of experimental and clinical studies. Front Neurol 4:79PubMedCentralPubMedCrossRef Tsitsopoulos PP, Marklund N (2013) Amyloid-beta peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: a review of experimental and clinical studies. Front Neurol 4:79PubMedCentralPubMedCrossRef
34.
Zurück zum Zitat Zemlan FP et al (2002) C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res 947(1):131–139PubMedCrossRef Zemlan FP et al (2002) C-tau biomarker of neuronal damage in severe brain injured patients: association with elevated intracranial pressure and clinical outcome. Brain Res 947(1):131–139PubMedCrossRef
35.
36.
Zurück zum Zitat Reddy N et al (1997) Characterization of a 15-lipoxygenase in human breast carcinoma BT-20 cells: stimulation of 13-HODE formation by TGF alpha/EGF. Biochem Biophys Res Commun 231(1):111–116PubMedCrossRef Reddy N et al (1997) Characterization of a 15-lipoxygenase in human breast carcinoma BT-20 cells: stimulation of 13-HODE formation by TGF alpha/EGF. Biochem Biophys Res Commun 231(1):111–116PubMedCrossRef
37.
Zurück zum Zitat Blask DE et al (2002) Light during darkness, melatonin suppression and cancer progression. Neuroendocrinol Lett 23(Suppl 2):52–56PubMed Blask DE et al (2002) Light during darkness, melatonin suppression and cancer progression. Neuroendocrinol Lett 23(Suppl 2):52–56PubMed
38.
Zurück zum Zitat Haas TA et al (1988) Binding of 13-HODE and 5-, 12- and 15-HETE to endothelial cells and subsequent platelet, neutrophil and tumor cell adhesion. Biochim Biophys Acta 961(2):153–159PubMedCrossRef Haas TA et al (1988) Binding of 13-HODE and 5-, 12- and 15-HETE to endothelial cells and subsequent platelet, neutrophil and tumor cell adhesion. Biochim Biophys Acta 961(2):153–159PubMedCrossRef
39.
Zurück zum Zitat Pasqualini ME et al (2003) Association between E-cadherin expression by human colon, bladder and breast cancer cells and the 13-HODE:15-HETE ratio. A possible role of their metastatic potential. Prostaglandins Leukot Essent Fat Acids 68(1):9–16CrossRef Pasqualini ME et al (2003) Association between E-cadherin expression by human colon, bladder and breast cancer cells and the 13-HODE:15-HETE ratio. A possible role of their metastatic potential. Prostaglandins Leukot Essent Fat Acids 68(1):9–16CrossRef
40.
Zurück zum Zitat Svennerholm L (1968) Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res 9(5):570–579PubMed Svennerholm L (1968) Distribution and fatty acid composition of phosphoglycerides in normal human brain. J Lipid Res 9(5):570–579PubMed
Metadaten
Titel
Increased cerebrospinal fluid cleaved tau protein (C-tau) levels suggest axonal damage in pediatric patients with brain tumors
verfasst von
Pelin Cengiz
Frank Zemlan
Jens C. Eickhoff
Richard Ellenbogen
Jerry J. Zimmerman
Publikationsdatum
01.08.2015
Verlag
Springer Berlin Heidelberg
Erschienen in
Child's Nervous System / Ausgabe 8/2015
Print ISSN: 0256-7040
Elektronische ISSN: 1433-0350
DOI
https://doi.org/10.1007/s00381-015-2705-7

Weitere Artikel der Ausgabe 8/2015

Child's Nervous System 8/2015 Zur Ausgabe

Wie erfolgreich ist eine Re-Ablation nach Rezidiv?

23.04.2024 Ablationstherapie Nachrichten

Nach der Katheterablation von Vorhofflimmern kommt es bei etwa einem Drittel der Patienten zu Rezidiven, meist binnen eines Jahres. Wie sich spätere Rückfälle auf die Erfolgschancen einer erneuten Ablation auswirken, haben Schweizer Kardiologen erforscht.

Hinter dieser Appendizitis steckte ein Erreger

23.04.2024 Appendizitis Nachrichten

Schmerzen im Unterbauch, aber sonst nicht viel, was auf eine Appendizitis hindeutete: Ein junger Mann hatte Glück, dass trotzdem eine Laparoskopie mit Appendektomie durchgeführt und der Wurmfortsatz histologisch untersucht wurde.

Mehr Schaden als Nutzen durch präoperatives Aussetzen von GLP-1-Agonisten?

23.04.2024 Operationsvorbereitung Nachrichten

Derzeit wird empfohlen, eine Therapie mit GLP-1-Rezeptoragonisten präoperativ zu unterbrechen. Eine neue Studie nährt jedoch Zweifel an der Notwendigkeit der Maßnahme.

Ureterstriktur: Innovative OP-Technik bewährt sich

19.04.2024 EAU 2024 Kongressbericht

Die Ureterstriktur ist eine relativ seltene Komplikation, trotzdem bedarf sie einer differenzierten Versorgung. In komplexen Fällen wird dies durch die roboterassistierte OP-Technik gewährleistet. Erste Resultate ermutigen.

Update Chirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

S3-Leitlinie „Diagnostik und Therapie des Karpaltunnelsyndroms“

Karpaltunnelsyndrom BDC Leitlinien Webinare
CME: 2 Punkte

Das Karpaltunnelsyndrom ist die häufigste Kompressionsneuropathie peripherer Nerven. Obwohl die Anamnese mit dem nächtlichen Einschlafen der Hand (Brachialgia parästhetica nocturna) sehr typisch ist, ist eine klinisch-neurologische Untersuchung und Elektroneurografie in manchen Fällen auch eine Neurosonografie erforderlich. Im Anfangsstadium sind konservative Maßnahmen (Handgelenksschiene, Ergotherapie) empfehlenswert. Bei nicht Ansprechen der konservativen Therapie oder Auftreten von neurologischen Ausfällen ist eine Dekompression des N. medianus am Karpaltunnel indiziert.

Prof. Dr. med. Gregor Antoniadis
Berufsverband der Deutschen Chirurgie e.V.

S2e-Leitlinie „Distale Radiusfraktur“

Radiusfraktur BDC Leitlinien Webinare
CME: 2 Punkte

Das Webinar beschäftigt sich mit Fragen und Antworten zu Diagnostik und Klassifikation sowie Möglichkeiten des Ausschlusses von Zusatzverletzungen. Die Referenten erläutern, welche Frakturen konservativ behandelt werden können und wie. Das Webinar beantwortet die Frage nach aktuellen operativen Therapiekonzepten: Welcher Zugang, welches Osteosynthesematerial? Auf was muss bei der Nachbehandlung der distalen Radiusfraktur geachtet werden?

PD Dr. med. Oliver Pieske
Dr. med. Benjamin Meyknecht
Berufsverband der Deutschen Chirurgie e.V.

S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“

Appendizitis BDC Leitlinien Webinare
CME: 2 Punkte

Inhalte des Webinars zur S1-Leitlinie „Empfehlungen zur Therapie der akuten Appendizitis bei Erwachsenen“ sind die Darstellung des Projektes und des Erstellungswegs zur S1-Leitlinie, die Erläuterung der klinischen Relevanz der Klassifikation EAES 2015, die wissenschaftliche Begründung der wichtigsten Empfehlungen und die Darstellung stadiengerechter Therapieoptionen.

Dr. med. Mihailo Andric
Berufsverband der Deutschen Chirurgie e.V.