Stefan Volkenstein

Spiral Ganglion Outgrowth and Hearing Development in p75NTR-Deficient Mice

To explore the role of nerve growth factor receptor p75NTR during the terminal neuronal development of the mammalian cochlea the onset of hearing and the in vitro response of spiral ganglion neurites to neurotrophin 3 (NT-3), which is known to play a critical role during neonatal inner ear development, were investigated in p75NTR-deficient mice (p75NTR–/–). Auditory-evoked brain stem response recordings from p75NTR–/– and wild-type (WT) littermates were measured from postnatal days (PD) 8 to 23. Additionally, spiral ganglion explants from p75NTR–/– and WT animals were dissected and cultured in an organotypic tissue culture system. In both groups, spiral ganglion neurite outgrowth was analyzed with and without NT-3 supplementation. No significant differences in the onset of hearing of mutant mice compared to the WT mice were detected, and both groups showed a similar development of hearing until PD 23. After stimulation with NT-3, neurite outgrowth was enhanced in both p75NTR–/– and WT mice. However, neurites from p75NTR–/– spiral ganglion explants were longer in both culture conditions. Moreover, NT-3 did not significantly enhance neurite number in p75NTR–/–, as it did in WT mice. P75NTR has a remarkable influence on spiral ganglion neurite growth behavior. However, p75NTR does not seem to be essential for the development of basic hearing function in the first 3 postnatal weeks.

Growth behavior of spiral ganglion explants on cochlear implant electrodes and their materials

BACKGROUND With the increasing use of cochlear implants (CIs), the insertion of alloplastic material into the inner ear is nowadays an established treatment for severe to profound hearing loss in children and adults. Beyond its widespread use, the biocompatibility of the CI electrode and its interaction with the neural structures of the cochlea is not yet established. METHODS To investigate the survival and growth behavior of spiral ganglion neurons on different CI materials, spiral ganglion explants from newborn rats were cultured on silicone and platinum, on a surface combination of silicone and platinum, and, finally, on a CI electrode. RESULTS The results of this study indicate that the growth of spiral ganglion neurons in vitro is strongly influenced by the different materials and their arrangement, with platinum exhibiting the highest degree of biocompatibility with respect to neurite extension. Level differences in the surface structure between silicone and platinum lead to inhibition of neurite outgrowth. Furthermore, the culturing of spiral ganglion explants on a CI electrode leads to neurite sprouting toward the electrodes made of platinum. CONCLUSION The biocompatibility of CI materials with spiral ganglion neurons was shown in this study, but it differs with different CI materials. Besides the material itself, the arrangement of the materials can affect the neurite extension.

Interaction of Cochlear Nucleus Explants With Semiconductor Materials

Objective/Hypothesis: Implantable hearing devices such as cochlear implants and auditory brainstem implants deliver auditory information through electrical stimulation of auditory neurons. The combination of microelectronic electrodes with auditory nerve cells may lead to further improvement of the hearing quality with these devices. Whereas several kinds of neurons are known to grow on semiconductor substrates, interactions of cochlear nucleus (CN) neurons with such materials have yet to be described.

Auditory development in progressive motor neuronopathy mouse mutants

The present study was performed to elucidate the hearing development in the progressive motor neuronopathy (pmn) mouse mutant. This mouse has been used as a model for human motoneuron disease. A missense mutation in the tubulin-specific chaperon E (Tbce) gene on mouse chromosome 13 was localized as the underlying genetic defect. The protein encoded by the Tbce gene is essential for the formation of primary tubulin complexes. Studies on motoneurons show disorganization in microtubules and disturbed axonal transport, followed by retrograde degeneration of the motoneurons. A similar pathomechanism is also possible for hearing disorders where disrupted microtubules could cause functional deficits in spiral ganglion neurons or in cochlear hair cells. Click auditory brainstem response (ABR) audiometry in homozygous pmn mutants showed a normal onset of hearing, but an increasing hearing threshold from postnatal day 26 (P26) on to death, compared to heterozygous mutants and wild-type mice. Histological sections of the cochlea at different ages showed a regular morphology. Additionally, spiral ganglion explants from mutant and wild-type mice were cultured. The neurite length from pmn mutants was shorter than in wild-type mice, and the neurite number/explant was significantly decreased in pmn mutants. We show that the pmn mouse mutant is a model for a progressive rapid hearing loss from P26 on, after initially normal hearing development. Heterozygous mice are not affected by this defect. With the knowledge of the well-known pathomechanism of this defect in motoneurons, a dysfunction of cellular mechanisms regulating tubulin assembling suggests that tubulin assembling plays an essential role in hearing function and maintenance.

Wachstumsanalyse von Spiralganglienexplantaten auf Kochleaimplantat-Elektroden und deren Materialkomponenten

BACKGROUND With the increasing use of cochlear implants (CIs), the insertion of alloplastic material into the inner ear is nowadays an established treatment for severe to profound hearing loss in children and adults. Beyond its widespread use, the biocompatibility of the CI electrode and its interaction with the neural structures of the cochlea is not yet established. METHODS To investigate the survival and growth behavior of spiral ganglion neurons on different CI materials, spiral ganglion explants from newborn rats were cultured on silicone and platinum, on a surface combination of silicone and platinum, and, finally, on a CI electrode. RESULTS The results of this study indicate that the growth of spiral ganglion neurons in vitro is strongly influenced by the different materials and their arrangement, with platinum exhibiting the highest degree of biocompatibility with respect to neurite extension. Level differences in the surface structure between silicone and platinum lead to inhibition of neurite outgrowth. Furthermore, the culturing of spiral ganglion explants on a CI electrode leads to neurite sprouting toward the electrodes made of platinum. CONCLUSION The biocompatibility of CI materials with spiral ganglion neurons was shown in this study, but it differs with different CI materials. Besides the material itself, the arrangement of the materials can affect the neurite extension.

Hearing development and spiral ganglion neurite growth in VASP deficient mice

Vasodilator-stimulated phosphoprotein (VASP) has been found to be involved in intracellular signalling pathways and to play an important role in the actin associated organization and formation of the cytoskeleton. Since differential VASP expression was noted in inner ear tissues, the present study was performed to investigate the hearing development in VASP deficient mice. Hearing development in VASP-/- mice and wild type animals was investigated by auditory brain stem (ABR) measurements. In addition, inner ear tissues of wild type animals were tested for VASP expression using PCR, Western blot analysis, in situ hybridisation, and immunohistochemistry. To compare spiral ganglion (SG) neurite growth, SG explants from VASP-/- and wild type mice were analyzed under cell culture conditions. The electroacoustical results of the present study indicate that VASP deficient mice present with a later onset of hearing during postnatal development compared to wild type animals. Transient VASP expression was detected in neonatal SG of wild type mice. Tissue culture experiments with SG explants from VASP-/- animals revealed significant alterations in SG neurite extension compared to wild types. The present findings suggest a role for VASP during neonatal development of the mammalian cochlea and allow speculation on a possible delayed innervation of cochlear hair cells due to changes in SG neurite growth in VASP-deficient mice. Temporary VASP deficits in the neonatal inner ear may be compensated by related proteins like MENA leading to a delayed but complete development of hearing function in VASP-/- animals.

Tympanoplastik Typ I im frühen Kindesalter erfolgsversprechend

Singh GB et al. Paediatric tympanoplasty: comparative study between patients aged 5–8 years and those aged over 14 years. J Laryngol Otol 2016; 130: 635–639.

Aktuelle Aspekte des kindlichen Cholesteatoms

ZusammenfassungCholesteatome lassen sich in genuine und erworbene Formen unterteilen. Während „epidermoid formations“ als Ursache des genuinen Cholesteatoms heutzutage allgemein anerkannt sind, werden bei der Pathogenese der erworbenen Form die Metaplasie-, Immigrations-, Proliferations- und Retraktionstaschentheorie diskutiert. Klinisch zeigt das kindliche Cholesteatom häufig ein ausgedehnteres und aggressiveres Wachstum als das des Erwachsenenalters. Molekularbiologische Unterschiede der Angiogenese, der Zytokinexpression und insbesondere ausgeprägtere Entzündungsreaktionen der Perimatrix können möglicherweise erste Erklärungsansätze hierfür bieten. Die chirurgische Therapie des Cholesteatoms im Kindesalter sollte individuell an den pathologischen Befund angepasst werden, wobei zumindest im Rahmen der Erstoperation einer geschlossenen Technik möglichst Vorrang eingeräumt werden sollte. Die Verfolgungstechnik der „inside-out mastoidectomy“ kann hier Vorteile einer guten intraoperativen Übersicht mit einem postoperativ physiologischen Gehörgang bieten.AbstractCholesteatomas can be subclassified into genuine and acquired forms. Whilst epidermoid formations are the generally accepted cause of genuine cholesteatomas, metaplasia, immigration, proliferation and retraction pocket theories have all been proposed to explain the development of acquired cholesteatomas. Clinically, paediatric cholesteatomas exhibit more extensive and aggressive growth than those arising in adulthood. Molecular biological differences in terms of angiogenesis, cytokine expression and particularly the more marked inflammatory responses of the perimatrix could potentially explain these clinical differences. The surgical therapy of paediatric cholesteatomas should be adapted to the individual pathological findings, although where possible a canal wall up procedure is preferred during initial surgery. The “inside-out” mastoidectomy tracking-technique combines the benefits of a good surgical overview with those of a physiological postoperative auditory canal.

Current aspects of paediatric cholesteatomas

ZusammenfassungCholesteatome lassen sich in genuine und erworbene Formen unterteilen. Während „epidermoid formations“ als Ursache des genuinen Cholesteatoms heutzutage allgemein anerkannt sind, werden bei der Pathogenese der erworbenen Form die Metaplasie-, Immigrations-, Proliferations- und Retraktionstaschentheorie diskutiert. Klinisch zeigt das kindliche Cholesteatom häufig ein ausgedehnteres und aggressiveres Wachstum als das des Erwachsenenalters. Molekularbiologische Unterschiede der Angiogenese, der Zytokinexpression und insbesondere ausgeprägtere Entzündungsreaktionen der Perimatrix können möglicherweise erste Erklärungsansätze hierfür bieten. Die chirurgische Therapie des Cholesteatoms im Kindesalter sollte individuell an den pathologischen Befund angepasst werden, wobei zumindest im Rahmen der Erstoperation einer geschlossenen Technik möglichst Vorrang eingeräumt werden sollte. Die Verfolgungstechnik der „inside-out mastoidectomy“ kann hier Vorteile einer guten intraoperativen Übersicht mit einem postoperativ physiologischen Gehörgang bieten.AbstractCholesteatomas can be subclassified into genuine and acquired forms. Whilst epidermoid formations are the generally accepted cause of genuine cholesteatomas, metaplasia, immigration, proliferation and retraction pocket theories have all been proposed to explain the development of acquired cholesteatomas. Clinically, paediatric cholesteatomas exhibit more extensive and aggressive growth than those arising in adulthood. Molecular biological differences in terms of angiogenesis, cytokine expression and particularly the more marked inflammatory responses of the perimatrix could potentially explain these clinical differences. The surgical therapy of paediatric cholesteatomas should be adapted to the individual pathological findings, although where possible a canal wall up procedure is preferred during initial surgery. The “inside-out” mastoidectomy tracking-technique combines the benefits of a good surgical overview with those of a physiological postoperative auditory canal.

Mucormycosis in paranasal sinuses

Three patients with mucormycosis of the paranasal sinuses were treated in the University ENT departments in Bochum and Essen in recent years. All patients were immunocompromised for different reasons and had reduced resistance against microorganism infection. They presented with symptoms of orbital complications of sinusitis. The further progress of these life-threatening fungal infections with a mortality rate between 35 and 70% depends on early and definitive diagnosis and radical surgical therapy to reduce the amount of infectious agent. The difficulties of early diagnosis by imaging, histology, microbiology, or molecular biology and postoperative therapeutic options especially with amphotericin B, liposomal amphotericin B, and posaconazole are illustrated and discussed.