Zusammenfassung
Das saure Gliafaserprotein („glial fibrillary acidic protein“, GFAP) ist ein hirnspezifisches Protein, das in Astrozyten in größeren Mengen exprimiert wird und wichtige Funktionen im Rahmen der Aufrechterhaltung des Zytoskeletts übernimmt. Nekrose und Zytolyse von astroglialen Zellen führen zur Freisetzung von GFAP in den Extrazellularraum und ins Blut. Hirnblutungen bedingen die unmittelbare mechanische Zelldestruktion, während bei Hirninfarkten Nekrose und Zytolyse histopathologisch in relevantem Ausmaß erst 6–12 h nach Symptombeginn zu finden sind. Insofern öffnet sich ein diagnostisches Fenster in den ersten Stunden nach dem Auftreten einer Schlaganfallsymptomatik, in dem erhöhte GFAP-Werte im Blut eine intrazerebrale Blutung anzeigen könnten. Diese Übersichtsarbeit beschreibt die dem Testprinzip zugrunde liegende Pathophysiologie und fasst die wesentlichen Ergebnisse der relevanten Forschungsarbeiten zusammen. Potenzielle Implikationen des GFAP-Tests wären die verbesserte prähospitale Triage von akuten Schlaganfallpatienten sowie die Möglichkeit, bei Patienten mit akuten Hirnblutungen rasch eine Therapie (Blutdrucksenkung, Gerinnungsausgleich bei antikoagulanzienassoziierter Blutung) einleiten zu können. Anderweitige mögliche Einsatzgebiete für GFAP liegen im Bereich der traumatischen Hirnschädigung und beim Glioblastom.
Summary
Glial fibrillary acidic protein (GFAP) is a highly brain-specific protein that is expressed in large quantities in astrocytes and has important functions in terms of maintaining and stabilizing the cytoskeleton. Acute intracerebral hemorrhage leads to an immediate mechanical destruction of astroglial cells with the subsequent release of GFAP into the extracellular space and the bloodstream. On the other hand, necrosis, cytolysis and GFAP release does not occur before 6–12 h after symptom onset in ischemic stroke. Thus, in the early hours after stroke increased GFAP values could indicate intracerebral hemorrhage. This review article describes the underlying pathophysiology of the test and guides the reader through the available data. Potential implications regarding the prehospital triage of acute stroke patients are discussed, including the possibility to initiate hyperacute treatment, such as blood pressure reduction in patients with intracerebral hemorrhage. Other areas of interest for a potential GFAP test include traumatic brain injury and malignant gliomas.
Literatur
Aguilar MI, Hart RG, Kase CS et al (2007) Treatment of warfarin-associated intracerebral hemorrhage: literature review and expert opinion. Mayo Clin Proc 82:82–92
Anderson CS, Heeley E, Huang Y et al (2013) Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med 368:2355–2365
Anderson RE, Hansson LO, Nilsson O et al (2001) High serum S100B levels for trauma patients without head injuries. Neurosurgery 48:1255–1258
Broderick JP, Palesch YY, Demchuk AM et al (2013) Endovascular therapy after intravenous t-PA versus t-PA alone for stroke. N Engl J Med 368:893–903
Brown TJ, Hess J, Shapiro L, Shaler RC (1993) Pregnancy protein-SP1: identification tool in forensic bloodstains. Can Soc Forensic Sci J 26:69–80
Brunkhorst RP, Pfeilschifter W, Foerch C (2010) Astroglial proteins as diagnostic markers of acute intracerebral hemorrhage – pathophysiological background and clinical findings. Transl Stroke Res 1:246–251
Bukhari W, Barnet MH, Prain K, Broadley SA (2012) Molecular pathogenesis of neuromyelitis optica. Int J Mol Sci 13:12970–12993
Diaz-Arrastia R, Wang KK, Papa L et al (2014) Acute biomarkers of traumatic brain injury: relationship between plasma levels of ubiquitin C-terminal hydrolase-L1 and glial fibrillary acidic protein. J Neurotrauma 31:19–25
Dvorak F, Haberer I, Sitzer M, Foerch C (2009) Characterisation of the diagnostic window of serum glial fibrillary acidic protein for the differentiation of intracerebral haemorrhage and ischaemic stroke. Cerebrovasc Dis 27:37–41
Eng LF, Ghirnikar RS, Lee YL (2000) Glial fibrillary acidic protein: GFAP-thirty-one years (1969–2000). Neurochem Res 25:1439–1451
Foerch C, Curdt I, Yan B et al (2006) Serum glial fibrillary acidic protein as a biomarker for intracerebral haemorrhage in patients with acute stroke. J Neurol Neurosurg Psychiatry 77:181–184
Foerch C, Niessner M, Back T et al (2012) Diagnostic accuracy of plasma glial fibrillary acidic protein for differentiating intracerebral hemorrhage and cerebral ischemia in patients with symptoms of acute stroke. Clin Chem 58:237–245
Foerch C, Wunderlich MT, Dvorak F et al (2007) Elevated serum S100B levels indicate a higher risk of hemorrhagic transformation after thrombolytic therapy in acute stroke. Stroke 38:2491–2495
Gladstone DJ, Rodan LH, Sahlas DJ et al (2009) A citywide prehospital protocol increases access to stroke thrombolysis in Toronto. Stroke 40:3841–3844
Herrmann M, Vos P, Wunderlich MT et al (2000) Release of glial tissue-specific proteins after acute stroke: a comparative analysis of serum concentrations of protein S-100B and glial fibrillary acidic protein. Stroke 31:2670–2677
Honda M, Tsuruta R, Kaneko T et al (2010) Serum glial fibrillary acidic protein is a highly specific biomarker for traumatic brain injury in humans compared with S-100B and neuron-specific enolase. J Trauma 69:104–109
Husain H, Savage W, Grossman SA et al (2012) Pre- and post-operative plasma glial fibrillary acidic protein levels in patients with newly diagnosed gliomas. J Neurooncol 109:123–127
Ilhan-Mutlu A, Wagner L, Widhalm G et al (2013) Exploratory investigation of eight circulating plasma markers in brain tumor patients. Neurosurgical review 36:45–55
Jung CS, Foerch C, Schanzer A et al (2007) Serum GFAP is a diagnostic marker for glioblastoma multiforme. Brain 130:3336–3341
Kaneko T, Kasaoka S, Miyauchi T et al (2009) Serum glial fibrillary acidic protein as a predictive biomarker of neurological outcome after cardiac arrest. Resuscitation 80:790–794
Lennon VA, Kryzer TJ, Pittock SJ et al (2005) IgG marker of optic-spinal multiple sclerosis binds to the aquaporin-4 water channel. J Exp Med 202:473–477
Lumpkins KM, Bochicchio GV, Keledjian K et al (2008) Glial fibrillary acidic protein is highly correlated with brain injury. J Trauma 65:778–782
Mayer CA, Brunkhorst R, Niessner M et al (2013) Blood levels of glial fibrillary acidic protein (GFAP) in patients with neurological diseases. PLoS One 8:e62101
McMullan JT, Knight WA, Clark JF et al (2010) Time-critical neurological emergencies: the unfulfilled role for point-of-care testing. Int J Emerg Med 3:127–131
Missler U, Wiesmann M, Wittmann G et al (1999) Measurement of glial fibrillary acidic protein in human blood: analytical method and preliminary clinical results. Clin Chem 45:138–141
Misu T, Takano R, Fujihara K et al (2009) Marked increase in cerebrospinal fluid glial fibrillar acidic protein in neuromyelitis optica: an astrocytic damage marker. J Neurol Neurosurg Psychiatry 80:575–577
Mondello S, Papa L, Buki A et al (2011) Neuronal and glial markers are differently associated with computed tomography findings and outcome in patients with severe traumatic brain injury: a case control study. Crit Care 15:R156
Nylen K, Csajbok LZ, Ost M et al (2007) Serum glial fibrillary acidic protein is related to focal brain injury and outcome after aneurysmal subarachnoid hemorrhage. Stroke 38:1489–1494
Pelinka LE, Kroepfl A, Schmidhammer R et al (2004) Glial fibrillary acidic protein in serum after traumatic brain injury and multiple trauma. J Trauma 57:1006–1012
Steiner T, Rosand J, Diringer M (2006) Intracerebral hemorrhage associated with oral anticoagulant therapy: current practices and unresolved questions. Stroke 37:256–262
Sun Y, Qin Q, Shang YJ et al (2013) The accuracy of glial fibrillary acidic protein in acute stroke differential diagnosis: a meta-analysis. Scand J Clin Lab Invest 73:601–606
Ting JY (2011) Letter to the editors: the potential role for prehospital thrombolysis and time-critical stroke transfers in the northern Norway aeromedical retrieval system; In response to: Norum J, Elsbak TM: air ambulance services in the Arctic: a Norwegian study. Int J Emerg Med 2011, 4:1. Int J Emerg Med 4:45
Unden J, Strandberg K, Malm J et al (2009) Explorative investigation of biomarkers of brain damage and coagulation system activation in clinical stroke differentiation. J Neurol 256:72–77
Vos PE, Jacobs B, Andriessen TM et al (2010) GFAP and S100B are biomarkers of traumatic brain injury: an observational cohort study. Neurology 75:1786–1793
Vos PE, Lamers KJ, Hendriks JC et al (2004) Glial and neuronal proteins in serum predict outcome after severe traumatic brain injury. Neurology 62:1303–1310
Wardlaw JM, Murray V, Berge E et al (2012) Recombinant tissue plasminogen activator for acute ischaemic stroke: an updated systematic review and meta-analysis. Lancet 379:2364–2372
Whiteley W, Tian Y, Jickling GC (2012) Blood biomarkers in stroke: research and clinical practice. Int J Stroke 7:435–439
Woertgen C, Rothoerl RD, Wiesmann M et al (2002) Glial and neuronal serum markers after controlled cortical impact injury in the rat. Acta Neurochir 81:205–207
Wunderlich MT, Wallesch CW, Goertler M (2006) Release of glial fibrillary acidic protein is related to the neurovascular status in acute ischemic stroke. Eur J Neurol 13:1118–1123
Zhang J, Zhang CH, Lin XL et al (2013) Serum glial fibrillary acidic protein as a biomarker for differentiating intracerebral hemorrhage and ischemic stroke in patients with symptoms of acute stroke: a systematic review and meta-analysis. Neurol Sci 34:1887–1892
Einhaltung ethischer Richtlinien
Interessenkonflikt. C. Foerch hat an vergüteten Advisory Boards der Fa. Roche Diagnostics zum Thema GFAP teilgenommen. Er hat Forschungsmittel der Fa. Roche Diagnostics für GFAP-Studien erhalten und ist Miterfinder des Patentes „Use of GFAP for identification of intracerebral hemorrhage“.W. Pfeilschifter, P. Zeiner und R. Brunkhorst geben an, dass kein Interessenkonflikt besteht. Der Beitrag enthält keine Studien an Menschen oder Tieren.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Foerch, C., Pfeilschifter, W., Zeiner, P. et al. Saures Gliafaserprotein beim Patienten mit akuten Schlaganfallsymptomen. Nervenarzt 85, 982–989 (2014). https://doi.org/10.1007/s00115-014-4128-1
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00115-014-4128-1