References of "Van de Water, T. R"
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See detailSupernumerary outer hair cells arise external to the last row of sensory cells in the organ of corti.
Lefèbvre, Philippe ULiege; Malgrange, Brigitte ULiege; Thiry, Marc ULiege et al

in Acta Oto-Laryngologica (2001), 121(2), 164-8

During the development of the mammalian inner ear, the number of hair cells produced is highly regulated and remains constant throughout life. The mechanism underlying this regulation is beginning to be ... [more ▼]

During the development of the mammalian inner ear, the number of hair cells produced is highly regulated and remains constant throughout life. The mechanism underlying this regulation is beginning to be understood although many aspects still remain obscure. When late embryonic or early postnatal rat organs of Corti were cultured, the production of supernumerary hair cells was observed. This overproduction of sensory cells could be modulated by the addition of several growth factors. In this study, we examined explants of rat organs of Corti that produced supernumerary hair cells. In the supernumerary hair cell region, up to two rows of inner hair cells and five rows of outer hair cells were observed. Morphological evaluation of these specimens revealed that less mature hair cells were located in the most external rows of these sensory cells. When a supernumerary hair cell was produced, a supporting cell (i.e. Deiters' cell) was also produced, strongly suggesting that the conversion of a Deiters' cell into a hair cell was not the mechanism that produced these extra hair cells. Based on these results, we propose that prosensory cells located at the external edge of the organ of Corti retain a capacity to form hair cells and that it is these prosensory cells that differentiate into supernumerary hair cells and Deiters' cells. [less ▲]

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See detailEpidermal Growth Factor Upregulates Production of Supernumerary Hair Cells in Neonatal Rat Organ of Corti Explants
Lefèbvre, Philippe ULiege; Malgrange, Brigitte ULiege; Thiry, Marc ULiege et al

in Acta Oto-Laryngologica (2000), 120(2), 142-5

The organ of Corti is highly ordered, with a single row of inner hair cells and three rows of outer hair cells. The number of hair cells produced was thought to be limited by the time of their terminal ... [more ▼]

The organ of Corti is highly ordered, with a single row of inner hair cells and three rows of outer hair cells. The number of hair cells produced was thought to be limited by the time of their terminal mitosis (i.e. E14 in the mouse). However, exogenous application of retinoic acid has been shown to stimulate the formation of supernumerary hair cells in organ of Corti explants from E13 to E16 mouse embryos. Using late embryonic and neonatal rat organ of Corti explants, we investigated the potential for production of supernumerary hair cells in more mature auditory sensory epithelia. When newborn rat organ of Corti explants were cultured under control conditions, an area of supernumerary hair cells was observed in a segment of organ of Corti that was at the junction between the basal and middle turns. In these areas of supernumerary hair cells the number of hair cells increased per unit of length, but remained constant per surface unit, further demonstrating the supernumerary character of this phenomenon. Organ of Corti explants treated with epidermal growth factor (EGF) showed a 50% increase in the length of the organ of Corti segment containing supernumerary hair cells. Upregulation of supernumerary hair cell formation by EGF was found to start and be maximal at birth (P0) and to disappear by 2 days after birth (P2). Treatment of EGF stimulated P0 explants with an antimitotic drug, cytosine arabinoside (ARAc), demonstrated that the production of supernumerary hair cells occurred independently of cell division. [less ▲]

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See detailConnexins, hearing and deafness: clinical aspects of mutations in the connexin 26 gene.
Lefèbvre, Philippe ULiege; Van De Water, T. R.

in Brain research. Brain research reviews (2000), 32(1), 159-62

Congenital deafness is a very frequent disorder occurring in approximately I in 1000 live births. Mutations in GJB2 encoding for gap junction protein connexin-26 (Cx26) have been established as the basis ... [more ▼]

Congenital deafness is a very frequent disorder occurring in approximately I in 1000 live births. Mutations in GJB2 encoding for gap junction protein connexin-26 (Cx26) have been established as the basis of autosomal recessive non-syndromic hearing loss and proposed in some rare cases of autosomal dominant form of deafness. Connexin are gap-junction proteins which constitute a major system of intercellular communication important in the exchange of electrolytes, second messengers and metabolites. In the inner ear, connexin 26 expression was demonstrated in the stria vascularis, basement membrane, limbus and the spiral prominence of the human cochlea. The loss of connexin 26 in the gap junction complex would expect to disrupt the recycling of potassium from the synapses at the base of hair cells through the supporting cells and fibroblasts of potassium ions back to the high potassium containing endolymph of the cochlear duct and therefore would result in a local intoxication of the Corti s organ by potassium, leading to the hearing loss. The discovery of the genes responsible of hearing loss in particular the identification of mutations in the gene coding for connexin 26 allows to hope some tremendous help in genetic counseling. The possible implication of the mutation of the connexin gene in the pathophysiology of some progressive adult deafness opens new prospects in the fine diagnostic of the ear diseases and eventually may lead to new therapeutic strategies applied to the cochlea. [less ▲]

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See detailExpression of Growth Factors and Their Receptors in the Postnatal Rat Cochlea
Malgrange, Brigitte ULiege; Rogister, Bernard ULiege; LEFEBVRE, Philippe ULiege et al

in Neurochemical Research (1998), 23(8), 1133-8

RT-PCR was used to assay for growth factors and receptors from seven different protein families in cochlea tissues of the juvenile rat. There was a broad representation of the growth factor families in ... [more ▼]

RT-PCR was used to assay for growth factors and receptors from seven different protein families in cochlea tissues of the juvenile rat. There was a broad representation of the growth factor families in all the cochlea tissues examined, though the organ of Corti and stria vascularis expressed a greater variety than the spiral ganglion. This broad expression suggests that a variety of known growth factors play significant roles in the development, maintenance, and repair of the inner ear. The results of this survey serve as a basis for the design of future in vitro experiments that will address the ability of growth factors to protect hair cells from damage and to evoke a repair-regeneration response by injured hair cells. [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 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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See detailNaftidrofuryl affects neurite regeneration by injured adult auditory neurons.
Lefèbvre, Philippe ULiege; Staecker, H.; Moonen, Gustave ULiege et al

in Acta Oto-Laryngologica (1993), 113(4), 498-501

Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a ... [more ▼]

Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations. [less ▲]

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See detailTgf Beta 1 Expression Is Initiated in Adult Auditory Neurons by Sectioning of the Auditory Nerve
LEFEBVRE, Philippe ULiege; Martin, Didier ULiege; Staecker, H. et al

in Neuroreport (1992), 3(4), 295-8

Neuronotrophic factors (e.g. basic fibroblast growth factor, bFGF and nerve growth factor, NGF) have been demonstrated to respectively promote survival and neuritogenesis in cultures of dissociated adult ... [more ▼]

Neuronotrophic factors (e.g. basic fibroblast growth factor, bFGF and nerve growth factor, NGF) have been demonstrated to respectively promote survival and neuritogenesis in cultures of dissociated adult rat spiral ganglia. Transforming growth factor beta (TGF beta 1) has been shown to modulate the response of cultured auditory neurons to bFGF through the induction of high affinity receptors for bFGF in the neurons. In this study, we show that TGF beta is expressed in situ by adult auditory neurons in response to traumatic injury (i.e. transection of the eighth cranial nerve). Based on these in vivo results and on the results from our previous in vitro studies, we propose that TFG beta 1 acts as an early autocrine signal involved in the response to injury by neurons of the peripheral auditor system. [less ▲]

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