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Laryngorhinootologie 2006; 85(10): 731-737
DOI: 10.1055/s-2006-925286
Otologie
© Georg Thieme Verlag KG Stuttgart · New York

Expression neurotropher Faktoren im Vestibularisschwannom - eine Übersicht

Neurotrophic Factor Expression in Vestibular SchwannomaM.  Diensthuber1 , T.  Lenarz1 , T.  Stöver1
  • 1Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde, Medizinische Hochschule Hannover, Hannover (Direktor: Prof. Dr. med. T. Lenarz)
Further Information

Publication History

Eingegangen: 4. August 2005

Angenommen: 15. Februar 2006

Publication Date:
10 April 2006 (online)

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Zusammenfassung

Das Vestibularisschwannom (Akustikusneurinom) ist ein in der Regel langsam wachsender, gutartiger Tumor, der aus den Schwann-Zellen des VIII. Hirnnervs hervorgeht. Für die Entstehung des Vestibularisschwannoms werden eine Reihe genetischer Faktoren diskutiert. Neben diesen molekularen Defekten deutet vieles darauf hin, dass das bemerkenswert variable Wachstumsverhalten der Vestibularisschwannome zusätzlich durch mitogene Stimuli gesteuert wird. Die unterschiedliche Expression neurotropher Faktoren im Gewebe des Vestibularisschwannoms stellt einen der möglichen Modulatoren dar, die auf die Entstehung und das Wachstum dieser Tumoren Einfluss nehmen könnten. Die Ergebnisse immunhistochemischer Untersuchungen belegen die Überexpression von Transforming Growth Factor-β (TGF-β) und Glial Cell Line-Derived Neurotrophic Factor (GDNF) im Vestibularisschwannom und liefern durch den Nachweis einer Coexpression Hinweise auf mögliche synergistische Interaktionen dieser beiden Nervenwachstumsfaktoren. Auch eine Reihe weiterer neurotropher Faktoren wie Nerve Growth Factor (NGF), Vascular Endothelial Growth Factor (VEGF), Epidermal Growth Factor (EGF), Fibroblast Growth Factor (FGF), Neuregulin (NRG) und Erythropoetin (EPO) werden im Vestibularisschwannom exprimiert und scheinen für das biologische und klinische Verhalten dieses Tumors von Bedeutung zu sein. Die vorliegende Arbeit gibt einen Überblick über das Expressionsmuster der einzelnen neurotrophen Faktoren, deren biologische Eigenschaften und Charakteristika sowie deren Rolle im Vestibularisschwannom.

Abstract

The vestibular schwannoma is a benign, slow-growing neoplasm that originates from the neurolemmal sheath of the vestibular branch of the VIIIth cranial nerve. This tumor entity accounts for 6 % of all intracranial tumors and the annual incidence of newly diagnosed vestibular schwannoma is reported as 13 per million. The molecular pathogenesis of both sporadic vestibular schwannoma and those occurring in neurofibromatosis type II appears to be associated with an aberration of a tumor suppressor gene on chromosome 22q12. The biological background for the various growth patterns of vestibular schwannoma is, however, largely unknown. This differing clinical and biological behaviour of vestibular schwannoma may be explained by the presence of neurotrophic factors. The results of recent immunohistochemical studies demonstrate the co-expression of transforming growth factor (TGF)-β 1 and glial cell line-derived neurotrophic factor (GDNF) in vestibular schwannoma and suggest a trophic synergism of both neurotrophic factors in this tumor. Moreover, expression of numerous different neurotrophic factors has been shown in studies of nerve growth factor (NGF), vascular endothelial growth factor (VEGF), epidermal growth factor (EGF), fibroblast growth factor (FGF), neuregulin (NRG) and erythropoietin (EPO) indicating a biological role in development, maintainance or growth of vestibular schwannoma. In this article, we summarize the findings on neurotrophic factor expression and discuss their characteristics and biological role in vestibular schwannoma.

Schlüsselwörter

Vestibularisschwannom - Akustikusneurinom - Wachstum - Wachstumsfaktoren - neurotrophe Faktoren

Key words

Vestibular schwannoma - growth - growth factors - neurotrophic factors

Literatur

  • 1 Irving R M, Moffat D A, Hardy D G, Barton D E, Xuereb J H, Maher E R. Somatic NF2 gene mutations in familial and non-familial vestibular schwannoma.  Hum Mol Genet. 1994;  3 347-350
    PubMedGoogle Scholar
  • 2 Moffat D A, Hardy D G, Irving R M, Viani L, Beynon G J, Baguley D M. Referral patterns in vestibular schwannomas.  Clin Otolaryngol. 1995;  20 80-83
    PubMedGoogle Scholar
  • 3 Ebadi M, Bashir R M, Heidrick M L, Hamada F M, Refaey H E, Hamed A, Helal G, Baxi M D, Cerutis D R, Lassi N K. Neurotrophins and their receptors in nerve injury and repair.  Neurochem Int. 1997;  30 347-374
    CrossrefPubMedGoogle Scholar
  • 4 Mattson M P, Cheng B, Smith-Swintosky V L. Mechanisms of neurotrophic factor protection against calcium- and free radical-mediated excitotoxic injury: implications for treating neurodegenerative disorders.  Exp Neurol. 1993;  124 89-95
    CrossrefPubMedGoogle Scholar
  • 5 Roberts A B, Sporn M B. The transforming growth factors βs. In: Sporn MB, Roberts AB (eds) Handbook of experimental pharmacology, Vol 95. Heidelberg; Springer 1991: 419-472
    Google Scholar
  • 6 Pirvola U, Ylikoski J, Palgi J, Lehtonen E, Arumae U, Saarma M. Brain-derived neurotrophic factor and neurotrophin 3 mRNAs in the peripheral target fields of developing inner ear ganglia.  Proc Natl Acad Sci USA. 1992;  89 9915-9919
    PubMedGoogle Scholar
  • 7 Wiechers B, Gestwa G, Mack A, Carroll P, Zenner H P, Knipper M. A changing pattern of brain-derived neurotrophic factor expression correlates with the rearrangement of fibers during cochlear development of rats and mice.  J Neurosci. 1999;  19 3033-3042
    PubMedGoogle Scholar
  • 8 Ylikoski J, Pirvola U, Virkkala J, Suvanto P, Liang X Q, Magal E, Altschuler R, Miller J M, Saarma M. Guinea pig auditory neurons are protected by glial cell line-derived growth factor from degeneration after noise trauma.  Hear Res. 1998;  124 17-26
    CrossrefPubMedGoogle Scholar
  • 9 Oestreicher E, Knipper M, Arnold A, Zenner H P, Felix D. Neurotrophin 3 potentiates glutamatergic responses of IHC afferents in the cochlea in vivo.  Eur J Neurosci. 2000;  12 1584-1590
    CrossrefPubMedGoogle Scholar
  • 10 Yancopoulos G D, Maisonpierre P C, Ip N Y, Aldrich T H, Belluscio L, Boulton T G, Cobb M H, Squinto S P, Furth M E. Neurotrophic factors, their receptors, and the signal transduction pathways they activate.  Cold Spring Harb Symp Quant Biol. 1990;  55 371-379
    PubMedGoogle Scholar
  • 11 Maran A G, Wilson J A, Gaze M N. The nature of the head and neck cancer.  Eur Arch Otorhinolaryngol. 1993;  250 127-132
    PubMedGoogle Scholar
  • 12 Levi-Montalcini R, Hamburger V. Selective growth stimulating effects of mouse sarcoma on the sensory and sympathetic nervous system of the chick embryo.  J Exp Zool. 1951;  116 321-361
    CrossrefPubMedGoogle Scholar
  • 13 Shu X Q, Mendell L M. Neurotrophins and hyperalgesia.  Proc Natl Acad Sci USA. 1999;  96 7693-7696
    CrossrefPubMedGoogle Scholar
  • 14 Levi-Montalcini R, Skaper S D, Dal Toso R, Petrelli L, Leon A. Nerve growth factor: from neurotrophin to neurokine.  Trends Neurosci. 1996;  19 514-520
    CrossrefPubMedGoogle Scholar
  • 15 Mattson M P, Mark R J. Excitotoxicity and excitoprotection in vitro.  Adv Neurol. 1996;  71 1-30
    PubMedGoogle Scholar
  • 16 Fabricant R N, Todaro G J, Eldridge R. Increased levels of a nerve-growth-factor cross-reacting protein in „central” neurofibromatosis.  Lancet. 1979;  1 4-7
    PubMedGoogle Scholar
  • 17 Matsunaga T, Hosoda Y, Kanzaki J. Ultrastructural localization of nerve growth factor receptor in acoustic neurinoma.  Acta Otolaryngol Suppl. 1991;  487 69-74
    PubMedGoogle Scholar
  • 18 Raivich G, Zimmermann A, Sutter A. The spatial and temporal pattern of beta NGF receptor expression in the developing chick embryo.  EMBO J. 1985;  4 637-644
    PubMedGoogle Scholar
  • 19 Yan Q, Johnson E M jr. A quantitative study of the developmental expression of nerve growth factor (NGF) receptor in rats.  Dev Biol. 1987;  121 139-148
    CrossrefPubMedGoogle Scholar
  • 20 Charabi S, Simonsen K, Charabi B, Jacobsen G K, Moos T, Rygaard J, Tos M, Thomsen J. Nerve growth factor receptor expression in heterotransplanted vestibular schwannoma in athymic nude mice.  Acta Otolaryngol. 1996;  116 59-63
    PubMedGoogle Scholar
  • 21 Yagi M, Kanzaki S, Kawamoto K, Shin B, Shah P P, Magal E, Sheng J, Raphael Y. Spiral ganglion neurons are protected from degeneration by GDNF gene therapy.  J Assoc Res Otolaryngol. 2000;  1 315-325
    PubMedGoogle Scholar
  • 22 Stöver T, Gong T L, Cho Y, Altschuler R A, Lomax M I. Expression of the GDNF family members and their receptors in the mature rat cochlea.  Brain Res Mol Brain Res. 2000;  76 25-35
    PubMedGoogle Scholar
  • 23 Stöver T, Nam Y, Gong T L, Lomax M I, Altschuler R A. Glial cell line-derived neurotrophic factor (GDNF) and its receptor complex are expressed in the auditory nerve of the mature rat cochlea.  Hear Res. 2001;  155 143-151
    CrossrefPubMedGoogle Scholar
  • 24 Stewart H J, Rougon G, Dong Z, Dean C, Jessen K R, Mirsky R. TGF-betas upregulate NCAM and L1 expression in cultured Schwann cells, suppress cyclic AMP-induced expression of O4 and galactocerebroside, and are widely expressed in cells of the Schwann cell lineage in vivo.  Glia. 1995;  15 419-436
    CrossrefPubMedGoogle Scholar
  • 25 Böttner M, Krieglstein K, Unsicker K. The transforming growth factor-betas: structure, signaling, and roles in nervous system development and functions.  J Neurochem. 2000;  75 2227-2240
    CrossrefPubMedGoogle Scholar
  • 26 Boyd F T, Massague J. Transforming growth factor-beta inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor.  J Biol Chem. 1989;  264 2272-2278
    PubMedGoogle Scholar
  • 27 Laiho M, Weis M B, Massague J. Concomitant loss of transforming growth factor (TGF)-beta receptor types I and II in TGF-beta-resistant cell mutants implicates both receptor types in signal transduction.  J Biol Chem. 1990;  265 18 518-18 524
    PubMedGoogle Scholar
  • 28 Rufer M, Flanders K, Unsicker K. Presence and regulation of transforming growth factor beta mRNA and protein in the normal and lesioned rat sciatic nerve.  J Neurosci Res. 1994;  39 412-423
    CrossrefPubMedGoogle Scholar
  • 29 Schubert D. Synergistic interactions between transforming growth factor beta and fibroblast growth factor regulate Schwann cell mitosis.  J Neurobiol. 1992;  23 143-148
    CrossrefPubMedGoogle Scholar
  • 30 Guenard V, Gwynn L A, Wood P M. Transforming growth factor-beta blocks myelination but not ensheathment of axons by Schwann cells in vitro.  J Neurosci. 1995;  15 419-428
    PubMedGoogle Scholar
  • 31 Ridley A J, Davis J B, Stroobant P, Land H. Transforming growth factors-beta 1 and beta 2 are mitogens for rat Schwann cells.  J Cell Biol. 1989;  109 3419-3424
    CrossrefPubMedGoogle Scholar
  • 32 Cardillo M R, Filipo R, Monini S, Aliotta N, Barbara M. Transforming growth factor-beta1 expression in human acoustic neuroma.  Am J Otol. 1999;  20 65-68
    PubMedGoogle Scholar
  • 33 Diensthuber M, Brandis A, Lenarz T, Stöver T. Co-expression of transforming growth factor-beta1 and glial cell line-derived neurotrophic factor in vestibular schwannoma.  Otol Neurotol. 2004;  25 359-365
    CrossrefPubMedGoogle Scholar
  • 34 Weerda H G, Gamberger T I, Siegner A, Gjuric M, Tamm E R. Effects of transforming growth factor-beta1 and basic fibroblast growth factor on proliferation of cell cultures derived from human vestibular nerve schwannoma.  Acta Otolaryngol. 1998;  118 337-343
    CrossrefPubMedGoogle Scholar
  • 35 Bizzarri M, Filipo R, Valente M G, Bernardeschi D, Ronchetti F, Monini S, Chiappini I, Barbara M. Release of transforming growth factor beta-1 in a vestibular schwannoma cell line.  Acta Otolaryngol. 2002;  122 785-787
    CrossrefPubMedGoogle Scholar
  • 36 Lin L F, Doherty D H, Lile J D, Bektesh S, Collins F. GDNF: a glial cell line-derived neurotrophic factor for midbrain dopaminergic neurons.  Science. 1993;  260 1130-1132
    PubMedGoogle Scholar
  • 37 Golden J P, Baloh R H, Kotzbauer P T, Lampe P A, Osborne P A, Milbrandt J, Johnson E M jr. Expression of neurturin, GDNF, and their receptors in the adult mouse CNS.  J Comp Neurol. 1998;  398 139-150
    PubMedGoogle Scholar
  • 38 Trupp M, Ryden M, Jornvall H, Funakoshi H, Timmusk T, Arenas E, Ibanez C F. Peripheral expression and biological activities of GDNF, a new neurotrophic factor for avian and mammalian peripheral neurons.  J Cell Biol. 1995;  130 137-148
    CrossrefPubMedGoogle Scholar
  • 39 Wefstaedt P, Scheper V, Lenarz T, Stöver T. Brain-derived neurotrophic factor/glial cell line-derived neurotrophic factor survival effects on auditory neurons are not limited by dexamethasone.  Neuroreport. 2005;  16 2011-2014
    CrossrefPubMedGoogle Scholar
  • 40 Jing S, Wen D, Yu Y, Holst P L, Luo Y, Fang M, Tamir R, Antonio L, Hu Z, Cupples R, Louis J C, Hu S, Altrock B W, Fox G M. GDNF-induced activation of the ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF.  Cell. 1996;  85 1113-1124
    CrossrefPubMedGoogle Scholar
  • 41 Treanor J J, Goodman L, de Sauvage F, Stone D M, Poulsen K T, Beck C D, Gray C, Armanini M P, Pollock R A, Hefti F, Phillips H S, Goddard A, Moore M W, Buj-Bello A, Davies A M, Asai N, Takahashi M, Vandlen R, Henderson C E, Rosenthal A. Characterization of a multicomponent receptor for GDNF.  Nature. 1996;  382 80-83
    CrossrefPubMedGoogle Scholar
  • 42 Durbec P, Marcos-Gutierrez C V, Kilkenny C, Grigoriou M, Wartiowaara K, Suvanto P, Smith D, Ponder B, Costantini F, Saarma M. et al . GDNF signalling through the Ret receptor tyrosine kinase.  Nature. 1996;  381 789-793
    CrossrefPubMedGoogle Scholar
  • 43 Iwase T, Jung C G, Bae H, Zhang M, Soliven B. Glial cell line-derived neurotrophic factor-induced signaling in Schwann cells.  J Neurochem. 2005;  94 1488-1499
    CrossrefPubMedGoogle Scholar
  • 44 Krieglstein K, Henheik P, Farkas L, Jaszai J, Galter D, Krohn K, Unsicker K. Glial cell line-derived neurotrophic factor requires transforming growth factor-beta for exerting its full neurotrophic potential on peripheral and CNS neurons.  J Neurosci. 1998;  18 9822-9834
    PubMedGoogle Scholar
  • 45 Schober A, Hertel R, Arumae U, Farkas L, Jaszai J, Krieglstein K, Saarma M, Unsicker K. Glial cell line-derived neurotrophic factor rescues target-deprived sympathetic spinal cord neurons but requires transforming growth factor-beta as cofactor in vivo.  J Neurosci. 1999;  19 2008-2015
    PubMedGoogle Scholar
  • 46 Dvorak H F, Brown L F, Detmar M, Dvorak A M. Vascular permeability factor/vascular endothelial growth factor, microvascular hyperpermeability, and angiogenesis.  Am J Pathol. 1995;  146 1029-1039
    PubMedGoogle Scholar
  • 47 Byrne A M, Bouchier-Hayes D J, Harmey J H. Angiogenic and cell survival functions of vascular endothelial growth factor (VEGF).  J Cell Mol Med. 2005;  9 777-794
    CrossrefPubMedGoogle Scholar
  • 48 Ferrara N, Alitalo K. Clinical applications of angiogenic growth factors and their inhibitors.  Nat Med. 1999;  5 1359-1364
    CrossrefPubMedGoogle Scholar
  • 49 Callagy G, Dimitriadis E, Harmey J, Bouchier-Hayes D, Leader M, Kay E. Immunohistochemical measurement of tumor vascular endothelial growth factor in breast cancer. A more reliable predictor of tumor stage than microvessel density or serum vascular endothelial growth factor.  Appl Immunohistochem Mol Morphol. 2000;  8 104-109
    CrossrefPubMedGoogle Scholar
  • 50 Neufeld G, Kessler O, Vadasz Z, Gluzman-Poltorak Z. The contribution of proangiogenic factors to the progression of malignant disease: role of vascular endothelial growth factor and its receptors.  Surg Oncol Clin N Am. 2001;  10 339-356
    PubMedGoogle Scholar
  • 51 Eatock M M, Schatzlein A, Kaye S B. Tumour vasculature as a target for anticancer therapy.  Cancer Treat Rev. 2000;  26 191-204
    CrossrefPubMedGoogle Scholar
  • 52 Nishikawa R, Cheng S Y, Nagashima R, Huang H J, Cavenee W K, Matsutani M. Expression of vascular endothelial growth factor in human brain tumors.  Acta Neuropathol. 1998;  96 453-462
    CrossrefPubMedGoogle Scholar
  • 53 Charabi S. Acoustic neuroma/vestibular schwannoma in vivo and in vitro growth models. A clinical and experimental study.  Acta Otolaryngol Suppl. 1997;  530 1-27
    PubMedGoogle Scholar
  • 54 Labit-Bouvier C, Crebassa B, Bouvier C, Andrac-Meyer L, Magnan J, Charpin C. Clinicopathologic growth factors in vestibular schwannomas: a morphological and immunohistochemical study of 69 tumours.  Acta Otolaryngol. 2000;  120 950-954
    Google Scholar
  • 55 Taylor C M, Weiss J B, Lye R H. Raised levels of latent collagenase activating angiogenesis factor (ESAF) are present in actively growing human intracranial tumours.  Br J Cancer. 1991;  64 164-168
    PubMedGoogle Scholar
  • 56 Brieger J, Bedavanija A, Lehr H A, Maurer J, Mann W J. Expression of angiogenic growth factors in acoustic neurinoma.  Acta Otolaryngol. 2003;  123 1040-1045
    CrossrefPubMedGoogle Scholar
  • 57 Caye-Thomasen P, Werther K, Nalla A, Bog-Hansen T C, Nielsen H J, Stangerup S E, Thomsen J. VEGF and VEGF receptor-1 concentration in vestibular schwannoma homogenates correlates to tumor growth rate.  Otol Neurotol. 2005;  26 98-101
    Google Scholar
  • 58 Cohen S. The stimulation of epidermal proliferation by a specific protein (EGF).  Dev Biol. 1965;  12 394-407
    CrossrefPubMedGoogle Scholar
  • 59 Shiurba R A, Eng L F, Vogel H, Lee Y L, Horoupian D S, Urich H. Epidermal growth factor receptor in meningiomas is expressed predominantly on endothelial cells.  Cancer. 1988;  62 2139-2144
    PubMedGoogle Scholar
  • 60 Sainsbury J R, Farndon J R, Needham G K, Malcolm A J, Harris A L. Epidermal-growth-factor receptor status as predictor of early recurrence of and death from breast cancer.  Lancet. 1987;  1 1398-1402
    PubMedGoogle Scholar
  • 61 Quon H, Liu F F, Cummings B J. Potential molecular prognostic markers in head and neck squamous cell carcinomas.  Head Neck. 2001;  23 147-159
    CrossrefPubMedGoogle Scholar
  • 62 Pallini R, Tancredi A, Casalbore P, Mercanti D, Larocca L M, Consales A, Lauretti L, Fernandez E. Neurofibromatosis type 2: growth stimulation of mixed acoustic schwannoma by concurrent adjacent meningioma: possible role of growth factors.  J Neurosurg. 1998;  89 149-154
    PubMedGoogle Scholar
  • 63 Sturgis E M, Woll S S, Aydin F, Marrogi A J, Amedee R G. Epidermal growth factor receptor expression by acoustic neuromas.  Laryngoscope. 1996;  106 457-462
    PubMedGoogle Scholar
  • 64 Itoh N, Ornitz D M. Evolution of the Fgf and Fgfr gene families.  Trends Genet. 2004;  20 563-569
    CrossrefPubMedGoogle Scholar
  • 65 Murphy P R, Myal Y, Sato Y, Sato R, West M, Friesen H G. Elevated expression of basic fibroblast growth factor messenger ribonucleic acid in acoustic neuromas.  Mol Endocrinol. 1989;  3 225-231
    PubMedGoogle Scholar
  • 66 Lefebvre P P, Staecker H, Weber T, Van de Water T R, Rogister B, Moonen G. TGFSS1 modulates bFGF receptor message expression in cultured adult auditory neurons.  Neuroreport. 1991;  2 305-308
    PubMedGoogle Scholar
  • 67 Flaumenhaft R, Moscatelli D, Saksela O, Rifkin D B. Role of extracellular matrix in the action of basic fibroblast growth factor: matrix as a source of growth factor for long-term stimulation of plasminogen activator production and DNA synthesis.  J Cell Physiol. 1989;  140 75-81
    CrossrefPubMedGoogle Scholar
  • 68 Nair S B, Leung H Y, Ince P, Ramsden R T, Wilson J A. Fibroblast growth factor receptor expression in vestibular schwannoma.  Clin Otolaryngol. 2000;  25 570-576
    PubMedGoogle Scholar
  • 69 Garratt A N, Britsch S, Birchmeier C. Neuregulin, a factor with many functions in the life of a schwann cell.  Bioessays. 2000;  22 987-996
    CrossrefPubMedGoogle Scholar
  • 70 Meyer D, Birchmeier C. Multiple essential functions of neuregulin in development.  Nature. 1995;  378 386-390
    CrossrefPubMedGoogle Scholar
  • 71 Wolpowitz D, Mason T B, Dietrich P, Mendelsohn M, Talmage D A, Role L W. Cysteine-rich domain isoforms of the neuregulin-1 gene are required for maintenance of peripheral synapses.  Neuron. 2000;  25 79-91
    CrossrefPubMedGoogle Scholar
  • 72 Taveggia C, Zanazzi G, Petrylak A, Yano H, Rosenbluth J, Einheber S, Xu X, Esper R M, Loeb J A, Shrager P, Chao M V, Falls D L, Role L, Salzer J L. Neuregulin-1 type III determines the ensheathment fate of axons.  Neuron. 2005;  47 681-694
    CrossrefPubMedGoogle Scholar
  • 73 Hansen M R, Linthicum F H jr. Expression of neuregulin and activation of erbB receptors in vestibular schwannomas: possible autocrine loop stimulation.  Otol Neurotol. 2004;  25 155-159
    PubMedGoogle Scholar
  • 74 Juul S E, Yachnis A T, Rojiani A M, Christensen R D. Immunohistochemical localization of erythropoietin and its receptor in the developing human brain.  Pediatr Dev Pathol. 1999;  2 148-158
    PubMedGoogle Scholar
  • 75 Bartesaghi S, Marinovich M, Corsini E, Galli C L, Viviani B. Erythropoietin: a novel neuroprotective cytokine.  Neurotoxicology. 2005;  26 923-928
    CrossrefPubMedGoogle Scholar
  • 76 Marti H H, Wenger R H, Rivas L A, Straumann U, Digicaylioglu M, Henn V, Yonekawa Y, Bauer C, Gassmann M. Erythropoietin gene expression in human, monkey and murine brain.  Eur J Neurosci. 1996;  8 666-676
    PubMedGoogle Scholar
  • 77 Falcioni M, Taibah A, De Donato G, Piccirillo E, Russo A, Sanna M. Fast-growing vestibular schwannoma.  Skull Base Surgery. 2000;  10 95-99
    PubMedGoogle Scholar
  • 78 Dillard D G, Venkatraman G, Cohen C, Delgaudio J, Gal A A, Mattox D E. Immunolocalization of erythropoietin and erythropoietin receptor in vestibular schwannoma.  Acta Otolaryngol. 2001;  121 149-152
    CrossrefPubMedGoogle Scholar

Priv.-Doz. Dr. med. Timo Stöver

Klinik und Poliklinik für Hals-Nasen-Ohrenheilkunde ·

Carl-Neuberg-Straße 1 · 30625 Hannover

Email: stoever.timo@mh-hannover.de

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