References of "Staecker, H"
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See detailLocal perfusion of the tumor necrosis factor alpha blocker infliximab to the inner ear improves autoimmune neurosensory hearing loss.
Van Wijk, F.; Staecker, H.; Keithley, E. et al

in Audiology and Neuro-otology (2006), 11(6), 357-65

OBJECTIVE: To evaluate the effect of transtympanic administration of tumor necrosis factor alpha (TNF-alpha) blockers to patients suffering from autoimmune inner ear disease (AIED). STUDY DESIGN ... [more ▼]

OBJECTIVE: To evaluate the effect of transtympanic administration of tumor necrosis factor alpha (TNF-alpha) blockers to patients suffering from autoimmune inner ear disease (AIED). STUDY DESIGN: Nonrandomized, prospective pilot study. SETTING: Tertiary referral center. PATIENTS: 9 patients (4 men and 5 women; aged 51.22 +/- 13.11 years) presenting with autoimmune sensorineural hearing loss who responded to oral steroid treatment. Two groups of patients were treated. Group A consisted of 5 patients with AIED who could not be tapered off steroids. Group B consisted of 4 patients who were treated with intratympanic anti-TNF-alpha antibody therapy alone after a relapse of hearing loss following discontinuation of steroids. INTERVENTION: A Silverstein MicroWick local delivery system was placed in the round window niche and the patients were treated for 4 weeks with a weekly infusion of infliximab, a monoclonal antibody against TNF-alpha. MAIN OUTCOME MEASURE(S): Evaluation of hearing thresholds at 250-8000 Hz was performed before and after implantation of the Silverstein MicroWick and local delivery of the TNF-alpha blocker. RESULTS: Local administration of the TNF-alpha blocker allowed methylprednisolone to be tapered off without loss of hearing function in 4/5 steroid-dependent patients. Four additional patients were treated only with anti-TNF-alpha perfusion to the round window membrane without concomitant systemic administration of methylprednisolone. In 3 of these 4 patients, the pure tone average improved to 22.6 +/- 15.7 dB, resulting in hearing recovery comparable to treatment with systemic methylprednisolone. The 7 responding patients showed a significant reduction of recurrence of hearing loss to 0.028 +/- 0.072 episodes per month over the 4.3 +/- 2.4 months of the post-treatment period compared to 0.84 +/- 0.4 recurrences per week seen in the pretreatment period. CONCLUSIONS: The results of this pilot trial demonstrate that in patients with AIED, transtympanic delivery of the TNF-alpha blocker infliximab once weekly for 4 weeks allowed steroids to be tapered off, resulted in hearing improvement and reduced disease relapses. These preliminary efficacy and safety results appear encouraging enough to warrant further follow-up and studies for better determination of the potential clinical utility of local administration of infliximab for autoimmune hearing loss. [less ▲]

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See detailCaspases, the enemy within, and their role in oxidative stress-induced apoptosis of inner ear sensory cells
Van De Water, T. R.; Lallemend, François; Eshraghi, A. A. et al

in Otology and Neurotology (2004), 25(4), 627-632

This review covers the general roles of members of the cysteine protease family of caspases in the process of apoptosis (programmed cell death) looking at their participation in both the "extrinsic" cell ... [more ▼]

This review covers the general roles of members of the cysteine protease family of caspases in the process of apoptosis (programmed cell death) looking at their participation in both the "extrinsic" cell death receptor and the "intrinsic" mitochondrial cell death pathways. It defines the difference between initiator and effector caspases and shows the progression of caspase activations that ends up in the apoptotic cell death and elimination of a damaged cell. The review then presents what is currently know about the participation of caspases in the programmed cell death of inner ear sensory cells during the process of normal development and maturation of the inner ear and their importance in this process as illustrated by the results of caspase-3 gene knockout experiments. The participation of specific caspases and the sequence of their activation in the elimination (apoptosis) of damaged sensory cells from adult inner ears after an injury that generates oxidative stress are reviewed. Both the possibility and the potential efficacy of caspase inhibition with a broad-spectrum pancaspase inhibitor as an interventional therapy to treat and rescue oxidative stress-damaged inner ear sensory cells from apoptosis are presented and discussed. [less ▲]

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See detailArrest of apoptosis in auditory neurons: Implications for sensorineural preservation in cochlear implantation
Scarpidis, U.; Madnani, D.; Shoemaker, C. et al

in Otology and Neurotology (2003), 24(3), 409-417

Hypothesis: The JNK/c-Jun cell death pathway is a major pathway responsible for the loss of oxidative stress-damaged auditory neurons. Background: Implantation of patients with residual hearing ... [more ▼]

Hypothesis: The JNK/c-Jun cell death pathway is a major pathway responsible for the loss of oxidative stress-damaged auditory neurons. Background: Implantation of patients with residual hearing accentuates the need to preserve functioning sensorineural elements. Although some auditory function may survive electrode insertion, the probability of initiating an ongoing loss of auditory neurons and hair cells is unknown. Cochlear implantation can potentially generate oxidative stress, which can initiate the cell death of both auditory neurons and hair cells. Methods: Dissociated cell cultures of P4 rat auditory neurons identified the apoptotic pathway initiated by oxidative stress insults (e.g., loss of trophic factor support) and characterized this pathway by arresting translation of pathway-specific mRNA with antisense oligonucleotide treatment and with the use of pathway specific inhibitors. The presence or absence of apoptosis-specific protein and changes in the level of neuronal survival measured the efficacy of these interventional strategies. Results: These in vitro studies identified the JNK/c-Jun cascade as a major initiator of apoptosis of auditory neurons in response to oxidative stress. Neurons pretreated with c-jun antisense oligonucleotide and exposed to high levels of oxidative stress were rescued from apoptosis, whereas neurons in treatment control cultures died. Treatment of oxidative-stressed cultures with either curcumin, a MAPKKK pathway inhibitor, or PD-098059, a MEK1 inhibitor, blocked loss of neurons via the JNK/c-Jun apoptotic pathway. Conclusion: Blocking the JNK/c-Jun cell death pathway is a feasible approach to treating oxidative stress-induced apoptosis within the cochlea and may have application as an otoprotective strategy during cochlear implantation. [less ▲]

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See detailAutoimmune sensorineural hearing loss improved by tumor necrosis factor-alpha blockade: a case report.
Staecker, H.; Lefèbvre, Philippe ULiege

in Acta Oto-Laryngologica (2002), 122(6), 684-7

Autoimmune inner ear disease is a treatable cause of sensorineural hearing loss and it is important for physicians and hearing health professionals to recognize that early diagnosis and proper management ... [more ▼]

Autoimmune inner ear disease is a treatable cause of sensorineural hearing loss and it is important for physicians and hearing health professionals to recognize that early diagnosis and proper management strategies may result in stabilization and improvement in hearing. The pathogenesis of autoimmune sensorineural hearing loss remains unclear but antibodies directed against the inner ear and/or cellular effectors have been proposed. Therefore, immunosuppressive drugs such as steroids and methotrexate are administered to interfere with the progression of hearing loss and in some cases have been found to improve hearing. We report herein the history of a patient who was treated by systemic administration of anti-tumor necrosis factor-alpha antibodies for Crohn's disease and who also had associated sensorineural hearing loss. Audiometric follow-up revealed not only the efficacy of tumor necrosis factor-alpha blockade in arresting the hearing loss but also an improvement in hearing of 15 dB on average across all frequencies. Hearing remained stable afterwards. [less ▲]

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See detailPharmacologic treatment of inner ear: from basic science to the patient.
Lefèbvre, Philippe ULiege; Staecker, H.; Van de Water, T. et al

in Acta Oto-Rhino-Laryngologica Belgica (2002), 56(1), 45-9

Most of the deafness are of sensorineural origin and are characterized by a loss of hair cells and of spiral ganglion neurons. At the present time, hearing aids are the only treatment. However, in some ... [more ▼]

Most of the deafness are of sensorineural origin and are characterized by a loss of hair cells and of spiral ganglion neurons. At the present time, hearing aids are the only treatment. However, in some diseases of the inner ear, pharmacological treatment have been proposed and used successfully. In this paper, we will review some basic science aspects of the biology of the neurosensory structures of the inner ear, in particular of the auditory neurons, that lead to the rationale of some treatments for the inner ear diseases. Developmental studies, neuronal cell culture experiments, and analyses of gene knockout animals reveal a number of growth factors which are important for the rescue and repair of injured auditory neurons in the inner ear. These factors rescue the injured auditory neurons in vivo. Furthermore, perfusion of antioxydant to the cochlea prevented the hearing loss induced by cisplatin. These in vitro and in vivo experiments demonstrate that it is possible to manipulate the neurosensory structures of the inner ear and provide an effective treatment to prevent the degeneration of the neurons. The molecules or drugs can be administered locally to the inner ear through a direct perilymphatic perfusion or through the round window membrane. As an example, we will discuss the treatment of patients suffering from idiopathic sensorineural hearing loss which can be treated successfully by a perfusion through the round window membrane, improving their hearing threshold and their speech discrimination. [less ▲]

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See detailMammalian auditory hair cell regeneration/repair and protection: a review and future directions.
Feghali, J. G.; Lefèbvre, Philippe ULiege; Staecker, H. et al

in Ear, Nose, and Throat Journal (1998), 77(4), 276280282-5

Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led ... [more ▼]

Regeneration/repair and protection of auditory hair cells and auditory neurons is an exciting, rapidly evolving field. Simultaneous developments in the fields of otobiology and surgical otology have led to new and exciting possibilities in inner ear medicine and surgery; specifically, the treatment or prevention of a variety of types of hearing losses in the foreseeable future. Sensorineural hearing loss in humans is commonly associated with a loss of auditory hair cells. It has been generally accepted that hearing loss resulting from hair cell damage is irreversible because the human ear has been considered to be incapable of regenerating or repairing these sensory elements following severe injury. An organ of Corti explant study has shown that it is possible to initiate the regeneration/repair of mammalian hair cells. In this study, ototoxin-damaged organ of Corti explants from juvenile rats were treated with a combination of retinoic acid (10-8M) and fetal calf serum (10%). TGF-alpha has been identified as a growth factor capable of evoking auditory hair cell regeneration/repair in ototoxin-damaged organ of Corti explants. Preliminary in vitro experiments with juvenile rat organ of Corti explants and in vivo studies in the cochleae of adult guinea pigs indicate that pretreatment followed by continuous treatment of the inner ear with a combination of retinoic acid and TGF-alpha can protect the auditory hair cells from the ototoxic effects of aminoglycosides. Because the integrity of spiral ganglion neurons is also essential for normal auditory function, there is a parallel series of in vitro and in vivo studies of the effects of neurotrophic factors on the survival of auditory neurons and the regeneration of injured neuronal processes. Clinical studies have demonstrated that it is now possible to perform surgeries on the inner ear, i.e., partial or total labyrinthectomies, and maintain hearing. The field of cochlear implantation has also provided insights into both the short- and long-term effects of cochlear fenestration on inner ear function. Administration of growth factors to the inner ears of animals is now possible with the use of implanted catheters and miniature infusion pumps. These advances suggest that localized application of drugs to the human inner ear may be feasible. The aim of this paper has been to provide an overview of advances in the study of the biology of auditory hair cells and auditory neurons, as well as recent relevant surgical advances. Taken together, these advances in otobiology and surgery will, in the future, be combined to devise new and innovative treatments for inner ear disorders. [less ▲]

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See detailCaspase inhibitors prevent cisplatin-induced apoptosis of auditory sensory cells.
Liu, W.; Staecker, H.; Stupak, H. et al

in Neuroreport (1998), 9(11), 2609-14

In vitro studies tested the efficacy of three caspase inhibitors, Ac-VAD-cmk (caspase-1 inhibitor), z-DEVD-fmk (caspase-3 inhibitor) and B-D-fmk (BOCDFK, a general inhibitor), for protecting auditory ... [more ▼]

In vitro studies tested the efficacy of three caspase inhibitors, Ac-VAD-cmk (caspase-1 inhibitor), z-DEVD-fmk (caspase-3 inhibitor) and B-D-fmk (BOCDFK, a general inhibitor), for protecting auditory sensory cells from cisplatin-damage induced loss. Treatment of 3-day-old rat organ of Corti explants with these caspase inhibitors protected > 80% of the auditory hair cells from cisplatin-damage initiated apoptosis. Dissociated cell cultures of 3-day-old rat spinal ganglia treated with any of these three caspase inhibitors in addition to exogenous neurotrophin have highly significant increases in neuronal survival following cisplatin exposure. These results indicate that loss of auditory sensory cells as a result of cisplatin-induced damage involves apoptosis and that blocking of this cell death pathway at the caspase level effectively rescues both hair cells and neurons. [less ▲]

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See detailIn vitro ototoxicity of aminoglycosides and platin derivatives. A semi-automatic assay for sensory hair cell damage in explanted rat organ of corti.
Malgrange, B.; LEFEBVRE, Philippe ULiege; van de Water, T.R. et al

in Toxicology in Vitro (1998), 12 (6)

The ototoxic damage that drugs such as neomycin, kanamycin, colistin, cisplatin, transplatin and carboplatin cause on outer and inner hair cells in postnatal day 3 rat cochlear explants was investigated ... [more ▼]

The ototoxic damage that drugs such as neomycin, kanamycin, colistin, cisplatin, transplatin and carboplatin cause on outer and inner hair cells in postnatal day 3 rat cochlear explants was investigated. Phalloidin-fluorescein conjugate-stained stereocilia bundles of sensory hair cells were quantified by video image analysis as a measurement of ototoxic effect. The video image quantification system established dose-response curves for ototoxic drugs (e.g. calculation of an IC50) and allowed comparisons between several ototoxins from the same family. This methodology provided the means to assess the efficacy of otoprotectant agents in preventing ototoxicity. Poly-l-aspartate (10-5M) and poly-l-glutamate (10-5M) protected auditory hair cells from neomycin (10-3M) toxicity while reduced glutathione (10-3M) provided protection against cisplatin (10-4M)-induced hair cell damage. [less ▲]

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See detailTransforming growth factor alpha treatment alters intracellular calcium levels in hair cells and protects them from ototoxic damage in vitro.
Staecker, H.; Dazert, S.; Malgrange, Brigitte ULiege et al

in International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience (1997), 15(4-5), 553-62

To determine if transforming growth factor alpha (TGF alpha) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair ... [more ▼]

To determine if transforming growth factor alpha (TGF alpha) pretreatment protects hair cells from aminoglycoside induced injury by modifying their intracellular calcium concentration, we assayed hair cell calcium levels in organ of Corti explants both before and after aminoglycoside (i.e. neomycin, 10(-3) M) exposure either with or without growth factor pretreatment. After TGF alpha (500 ng/ml) treatment, the intracellular calcium level of hair cells showed a five-fold increase as compared to the levels observed in the hair cells of control cultures. After ototoxin exposure, calcium levels in hair cells of control explants showed an increase relative to their baseline levels, while in the presence of growth factors pretreatment, hair cells showed a relative reduction in calcium levels. Pretreatment of organ of Corti explants afforded significant protection of hair cell stereocilia bundle morphology from ototoxic damage when compared to explants exposed to ototoxin alone. This study correlates a rise in hair cell calcium levels with the otoprotection of hair cells by TGF alpha in organ of Corti explants. [less ▲]

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See detailProtection of both auditory hair cells and auditory neurons from cisplatin induced damage.
Gabaizadeh, R.; Staecker, H.; Liu, W. et al

in Acta Oto-Laryngologica (1997), 117(2), 232-8

Cisplatin is an effective anti-neoplastic agent used in the treatment of squamous cell cancer of the head and neck, but with serious side effects. One serious side effect is damage to both the auditory ... [more ▼]

Cisplatin is an effective anti-neoplastic agent used in the treatment of squamous cell cancer of the head and neck, but with serious side effects. One serious side effect is damage to both the auditory hair cells and the auditory neurons. The damage to the neurons has been shown to be a direct effect and not due to the loss of the neurotrophic support provided by the hair cells. Several neurotrophins have been shown to lessen the extent of cisplatin induced damage of auditory neurons in vitro, but these neurotrophins have had no effect on the extent of damage to the hair cells. D-methionine (D-met) has been demonstrated to provide protection against cisplatin's nephrotoxicity in vivo and ototoxicity in vitro. In this study the combination of brain derived neurotrophic factor (BDNF) with D-met has shown that both auditory neurons and auditory hair cells can be protected from cisplatin induced damage in vitro. These results demonstrate that this type of combination therapy (i.e. a neurotrophin combined with a free radical scavenger) can provide more complete protection for the auditory receptor against cisplatin toxicity than either of these agents alone. Because both BDNF and D-met have been shown to have trophic activity in vitro we proposed that the combination of these agents will also provide effective protection against cisplatin induced ototoxicity and neurotoxicity of the auditory receptor in vivo. [less ▲]

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See detailNt-3 Has a Tropic Effect on Process Outgrowth by Postnatal Auditory Neurones in Vitro
Malgrange, Brigitte ULiege; LEFEBVRE, Philippe ULiege; Martin, Didier ULiege et al

in Neuroreport (1996), 7(15-17), 2495-9

CONFOCAL analysis of early postnatal auditory neurones in a bicompartmental culture system was used to test for chemoattractant properties of NGF, BDNF and NT-3 on neuronal process outgrowth. NT-3 exerted ... [more ▼]

CONFOCAL analysis of early postnatal auditory neurones in a bicompartmental culture system was used to test for chemoattractant properties of NGF, BDNF and NT-3 on neuronal process outgrowth. NT-3 exerted a strong tropic effect on neuritic outgrowth from auditory neurones in this system. BDNF and NGF did not have any tropic activity that directed processes outgrowth from auditory neurones. However, BDNF was important for the support of neuronal survival in NGF-treated cultures and for neuritogenesis in NT-3-treated cultures. Since NT-3 has been identified as both a survival factor and a chemotropic agent for auditory neurones, it is likely that this neurotrophin will be a useful therapeutic agent in the treatment of damaged cochleae for the recovery of hearing. [less ▲]

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See detailNT-3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells.
Staecker, H.; Kopke, R.; Malgrange, Brigitte ULiege et al

in Neuroreport (1996), 7(4), 889-94

Destruction of auditory hair cells results in a subsequent loss of auditory neurons. In situ hybridization and neuronal cell culture studies as well as analyses of the inner ears of neurotrophin and ... [more ▼]

Destruction of auditory hair cells results in a subsequent loss of auditory neurons. In situ hybridization and neuronal cell culture studies as well as analyses of the inner ears of neurotrophin and neurotrophin receptor gene knockout mice have shown that NT-3 and BDNF mediate both the development and survival of auditory neurons. In this study guinea pigs were exposed to the ototoxic combination of an aminoglycoside antibiotic and a loop diuretic and then received 8 weeks of intracochlear infusion of either NT-3, BDNF or NT-3 + BDNF to determine whether site-specific application of these neurotrophins could prevent the loss of auditory neurons that follows a loss of auditory hair cells. Infusion of either NT-3 or NT-3 + BDNF into the scala tympani resulted in a > 90% survival of auditory neurons while BDNF infusion yielded a 78% survival rate, compared with a 14-24% neuronal survival rate in untreated ototoxin-exposed cochleae. These results show that loss of auditory neurons that occurs subsequent to a loss of auditory hair cells can be prevented by in vivo neurotrophin therapy with either NT-3 or BDNF. [less ▲]

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See detailThe role of the neurotrophins in maturation and maintenance of postnatal auditory innervation.
Staecker, H.; Galinovic-Schwartz, V.; Liu, W. et al

in American Journal of Otology (1996), 17(3), 486-92

Auditory hair cells produce trophic factors that directly affect maturation and survival of auditory neurons. These factors include two members of the neurotrophin family: brain-derived neurotrophic ... [more ▼]

Auditory hair cells produce trophic factors that directly affect maturation and survival of auditory neurons. These factors include two members of the neurotrophin family: brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3). Loss of hair cells, as a result of either noise trauma or ototoxic damage, results in the degeneration of auditory neurons. An in vitro model of early postnatal rat organ of Corti/spiral ganglion explants was used to study the effects of deprivation and supplementation of nerve growth factor (NGF), BDNF, and NT-3 on neuronal survival. Immunolocalization of receptors for these neurotrophins correlated with their effectiveness as promoters of neuronal survival. BDNF affected early neuronal survival, whereas NT-3 was the most important survival factor for maturing auditory neurons. NGF was shown to maintain axonal morphology. Our results support the hypothesis that changes in the expression of these neurotrophins and their specific receptors in the maturing cochlea may control the postnatal processes of neuronal apoptosis and maturation of the innervation of both inner and outer hair cells. The results suggest that these growth factors have potential for preventing neuronal degeneration as well as enhancing the repair of damaged neuronal processes in the traumatized auditory system. [less ▲]

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See detailNGF, BDNF and NT-3 play unique roles in the in vitro development and patterning of innervation of the mammalian inner ear.
Staecker, H.; Van De Water, T. R.; Lefèbvre, Philippe ULiege et al

in Brain research. Developmental brain research (1996), 92(1), 49-60

Developing cochleovestibular ganglion (CVG) neurons depend upon interaction with the otocyst, their peripheral target tissue, for both trophic support and tropic guidance. RT-PCR of E11 through E14 ... [more ▼]

Developing cochleovestibular ganglion (CVG) neurons depend upon interaction with the otocyst, their peripheral target tissue, for both trophic support and tropic guidance. RT-PCR of E11 through E14 otocyst-CVG RNA extracts have shown that NGF as well as BDNF and NT-3 are expressed in the developing inner ear (in situ RT-PCR on tissue sections of E12 otocysts localized all three neurotrophins to the otocyst). To evaluate the functional significance of NGF, BDNF and NT-3 expression, E10.5 otocyst-CVG explants were treated with antisense oligonucleotides and compared to sense treated and control cultures. Confocal microscopic analysis revealed that treatment with BDNF antisense resulted in extensive neuronal cell death, downregulation of NGF caused an inhibition of neuritogenesis and a decrease in the neuronal population of the CVG, whereas treatment with NT-3 antisense resulted in a loss of target directed CVG neuritic ingrowth in this in vitro model. The effect of NGF or BDNF antisense treatment could be prevented by the simultaneous addition of the respective growth factor. These findings demonstrate that each of the three neurotrophins have important roles during the onset of neuritic ingrowth of the CVG neurons to the otocyst. [less ▲]

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See detailEffects of neurotrophins on early auditory neurones in cell culture.
Malgrange, Brigitte ULiege; Lefèbvre, Philippe ULiege; Van de Water, T. R. et al

in Neuroreport (1996), 7(4), 913-7

During the first week of postnatal development, the innervation of the organ of Corti changes from an immature to an adult pattern. Dissociated cell cultures of early postnatal spiral ganglia were used to ... [more ▼]

During the first week of postnatal development, the innervation of the organ of Corti changes from an immature to an adult pattern. Dissociated cell cultures of early postnatal spiral ganglia were used to investigate the effects of nerve growth factor (NGF), brain derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) on maturing auditory neurones. BDNF was the most potent stimulator of neuritogenesis, NT-3 provided the strongest support for neuronal survival, while NGF supported limited neuritogenesis, and only at pharmacological levels. These findings suggest that both BDNF and NT-3 participate in the postnatal maturation of cochlear innervation and that NGF is most probably not involved in this process. [less ▲]

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See detailNeurotrophic effects of BDNF and CNTF, alone and in combination, on postnatal day 5 rat acoustic ganglion neurons.
Hartnick, C. J.; Staecker, H.; Malgrange, Brigitte ULiege et al

in Journal of Neurobiology (1996), 30(2), 246-54

The neuronal survival promoting ability of brain derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF), individually and in combination, was evaluated in dissociated cell cultures of ... [more ▼]

The neuronal survival promoting ability of brain derived neurotrophic factor (BDNF), and ciliary neurotrophic factor (CNTF), individually and in combination, was evaluated in dissociated cell cultures of postnatal day 5 (P5) rat acoustic ganglia. The neuritogenic promoting effect of these same neurotrophic factors was examined in organotypic explants of P5 rat acoustic ganglia. The results showed that BDNF was maximally effective at a concentration of 10 ng/mL in promoting both survival and neuritogenesis of these postnatal auditory neurons in vitro. CNTF was maximally effective at a concentration of 0.01 ng/mL at promoting both survival and neuritogenesis in the acoustic ganglion cultures. BDNF had its strongest effect on neuronal survival while CNTF was most effective in stimulating neurite outgrowth. These two neurotrophic factors, when added together at their respective maximally effective concentrations, behave in an additive manner for promoting both survival and neuritic outgrowth by the auditory neurons. [less ▲]

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See detailEffect of neurotrophic factors on the inner ear: clinical implications.
Kopke, R.; Staecker, H.; Lefèbvre, Philippe ULiege et al

in Acta Oto-Laryngologica (1996), 116(2), 248-52

Loss of auditory neurons is commonly associated with sensorineural deafness, and may result from either direct neuronal injury or be a consequence of sensory hair cell loss (i.e. loss of source of trophic ... [more ▼]

Loss of auditory neurons is commonly associated with sensorineural deafness, and may result from either direct neuronal injury or be a consequence of sensory hair cell loss (i.e. loss of source of trophic factors). Developmental studies and in vitro studies of adult neurons have begun to identify growth factors important for the development, maintenance, and rescue/repair of auditory neurons. Specific neurotrophic factors have been shown to enhance the auditory neurons' ability to withstand traumatic loss of target tissue connections and toxic injury. Promising initial in vivo studies confirm that specific neurotrophins are able to support neuronal survival and promote neuronal repair in an intact animal following injury to the cochlea. Further study into unique methods and routes of growth factor delivery will provide insights into the possibility of neurotrophic growth factors to act as drugs for the treatment of injured or stressed auditory neurons. [less ▲]

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See detailNT-3 combined with CNTF promotes survival of neurons in modiolus-spiral ganglion explants.
Staecker, H.; Liu, W.; Hartnick, C. et al

in Neuroreport (1995), 6(11), 1533-7

Auditory neurons depend upon the integrity of both their peripheral (auditory hair cells) and central (cochlear nucleus) targets for survival. One proposed trophic mechanism is the production of ... [more ▼]

Auditory neurons depend upon the integrity of both their peripheral (auditory hair cells) and central (cochlear nucleus) targets for survival. One proposed trophic mechanism is the production of neurotrophin-3 (NT-3) by auditory hair cells. Modiolus-spiral ganglion explants from adult rats that closely mirror cell-cell interactions and in vivo tissue relationships within this ganglion provide a model for testing trophic factors. Brain derived neurotrophic factor (BDNF), NT-3 and ciliary neurotrophic factor (CNTF) were tested for their ability, both individually and in combination, to support neuronal survival. NT-3 was the strongest individual promoter of survival, while CNTF (a cytokine) with NT-3 (a neurotrophin) was the most effective combination for promoting the survival of auditory neurons. [less ▲]

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See detailNeurotrophins affect survival and neuritogenesis by adult injured auditory neurons in vitro.
Lefèbvre, Philippe ULiege; Malgrange, Brigitte ULiege; Staecker, H. et al

in Neuroreport (1994), 5(8), 865-8

This study evaluates the trophic effects of three neurotrophins on traumatized adult auditory neurons in culture, and the presence of these neurotrophins in cochlear nucleus tissue. BDNF and NT-3 promoted ... [more ▼]

This study evaluates the trophic effects of three neurotrophins on traumatized adult auditory neurons in culture, and the presence of these neurotrophins in cochlear nucleus tissue. BDNF and NT-3 promoted survival but very limited neuritogenesis by adult auditory neurons in vitro, while NGF, although without a survival effect, evoked a robust neuritic outgrowth response when combined with BDNF. Messenger RNAs that encode for NGF, BDNF and NT-3 were detected by RT-PCR in RNA extracts from adult cochlear nuclei tissue. Based on these in vitro and in vivo findings, we propose NT-3 as the agent of the peripheral target-derived survival promoting effect and NGF, BDNF, and NT-3 as mediators of trophic influences originating from the central target (i.e. cochlear nucleus). [less ▲]

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See detailRetinoic Acid Stimulates Regeneration of Mammalian Auditory Hair Cells
Lefèbvre, Philippe ULiege; Malgrange, Brigitte ULiege; Staecker, H. et al

in Science (1993), 260(5108), 692-5

Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro ... [more ▼]

Sensorineural hearing loss resulting from the loss of auditory hair cells is thought to be irreversible in mammals. This study provides evidence that retinoic acid can stimulate the regeneration in vitro of mammalian auditory hair cells in ototoxic-poisoned organ of Corti explants in the rat. In contrast, treatment with retinoic acid does not stimulate the formation of extra hair cells in control cultures of Corti's organ. Retinoic acid-stimulated hair cell regeneration can be blocked by cytosine arabinoside, which suggests that a period of mitosis is required for the regeneration of auditory hair cells in this system. These results provide hope for a recovery of hearing function in mammals after auditory hair cell damage. [less ▲]

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