References of "Malgrange, Brigitte"
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See detailMechanisms of cell death in the injured auditory system: Otoprotective strategies
Lefèbvre, Philippe ULg; Malgrange, Brigitte ULg; Lallemend, François et al

in Audiology & Neuro-otology (2002), 7(3, May-Jun), 165-170

Oxidative stress insults such as neurotrophin withdrawal, sound trauma, hypoxia/ischemia, ototoxic antibiotics, and chemotherapeutic agents have been shown to induce apoptosis of both auditory hair cells ... [more ▼]

Oxidative stress insults such as neurotrophin withdrawal, sound trauma, hypoxia/ischemia, ototoxic antibiotics, and chemotherapeutic agents have been shown to induce apoptosis of both auditory hair cells and neurons. In this paper, we review some components of the apoptotic pathways leading to the death of hair cells and auditory induced by growth factor withdrawal or cisplatin intoxication: (1) reactive oxygen species and free radicals are formed as by-products of several metabolic pathways and these molecules can themselves cause cell damage by reacting with cellular proteins; (2) activation of caspases, and (3) activation of calpain. These mechanisms have several different points at which inhibitors could be targeted to protect cells from programmed cell death, including the prevention of oxidative stress-induced apoptosis and the activation of caspases and calpains. Copyright (C) 2002 S. Karger AG, Basel. [less ▲]

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See detailNeurotransmitters as Early Signals for Central Nervous System Development
Nguyen, Laurent ULg; Rigo, Jean-Michel; Rocher, Véronique et al

in Cell & Tissue Research (2001), 305(2), 187-202

During brain ontogenesis, the temporal and spatial generation of the different types of neuronal and glial cells from precursors occurs as a sequence of successive progenitor stages whose proliferation ... [more ▼]

During brain ontogenesis, the temporal and spatial generation of the different types of neuronal and glial cells from precursors occurs as a sequence of successive progenitor stages whose proliferation, survival and cell-fate choice are controlled by environmental and cellular regulatory molecules. Neurotransmitters belong to the chemical microenvironment of neural cells, even at the earliest stages of brain development. It is now established that specific neurotransmitter receptors are present on progenitor cells of the developing central nervous system and could play, during neural development, a role that has remained unsuspected until recently. The present review focuses on the occurrence of neurotransmitters and their corresponding ligand-gated ion channel receptors in immature cells, including neural stem cells of specific embryonic and neonatal brain regions. We summarize in vitro and in vivo data arguing that neurotransmitters could regulate morphogenetic events such as proliferation, growth, migration, differentiation and survival of neural precursor cells. The understanding of neurotransmitter function during early neural maturation could lead to the development of pharmacological tools aimed at improving adult brain repair strategies. [less ▲]

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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 ULg; Malgrange, Brigitte ULg; Thiry, Marc ULg 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 detailPeripheral Nerve Regeneration Using Bioresorbable Macroporous Polylactide Scaffolds
Maquet, Véronique; Martin, Didier ULg; Malgrange, Brigitte ULg et al

in Journal of Biomedical Materials Research, Part A (2000), 52(4), 639-51

The ability of DRG-derived neurons to survive and attach onto macroporous polylactide (PLA) foams was assessed in vitro. The foams were fabricated using a thermally induced polymer-solvent phase ... [more ▼]

The ability of DRG-derived neurons to survive and attach onto macroporous polylactide (PLA) foams was assessed in vitro. The foams were fabricated using a thermally induced polymer-solvent phase separation. Two types of pore structures, namely oriented or interconnected pores, can be produced, depending on the mechanism of phase separation, which in turn can be predicted by the thermodynamics of the polymer-solvent pair. Coating of the porous foams with polyvinylalcohol (PVA) considerably improved the wettability of the foams and allowed for cell culture. The in vitro biocompatibility of the PVA-coated supports was demonstrated by measuring cell viability and neuritogenesis. Microscopic observations of the cells seeded onto the polymer foams showed that the interconnected pore networks were more favorable to cell attachment than the anisotropic ones. The capacity of highly oriented foams to support in vivo peripheral nerve regeneration was studied in rats. A sciatic nerve gap of 5-mm length was bridged with a polymer implant showing macrotubes of 100 microm diameter. At 4 weeks postoperatively, the polymer implant was still present. It was well integrated and had restored an anatomic continuity. An abundant cell migration was observed at the outer surface of the polymer implant, but not within the macrotubes. This dense cellular microenvironment was found to be favorable for axogenesis. [less ▲]

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See detailPharmacological Modulation of the Bystander Effect in the Herpes Simplex Virus Thymidine Kinase/Ganciclovir Gene Therapy System: Effects of Dibutyryl Adenosine 3',5'-Cyclic Monophosphate, Alpha-Glycyrrhetinic Acid, and Cytosine Arabinoside
Robe, Pierre ULg; Princen, Frédéric; Martin, Didier ULg et al

in Biochemical Pharmacology (2000), 60(2), 241-9

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield ... [more ▼]

The herpes simplex virus type 1 thymidine kinase (HSV1-tk) suicide gene/ganciclovir system was first applied to the treatment of glioblastoma tumors, but was hampered by the low gene transfection yield. Fortunately, the gap junction-dependent diffusion of phosphorylated ganciclovir metabolites from transfected cells to their neighbors proved to enhance the overall benefit of this strategy. However, as tumor cells are often gap junction-deficient, we sought to restore this property pharmacologically and hence to improve the efficacy of the treatment. We demonstrated that this approach was feasible in glioblastoma cells using dibutyryl adenosine 3',5'-cyclic monophosphate (cAMP) (100 microM) as a pharmacological inducer of gap junctions. alpha-Glycyrrhetinic acid (25 microM), on the other hand, strongly inhibited both gap junction-mediated intercellular communication and the bystander effect, thus confirming the role of gap junctions in HSV-tk-mediated bystander killing. Using cytosine arabinoside as a growth inhibitor, we underlined the role of tumor cell proliferation in the sensitivity of HSV-tk-transfected cells to ganciclovir and demonstrated its correlation with the importance of the bystander effect. [less ▲]

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See detailGlycine Triggers an Intracellular Calcium Influx in Oligodendrocyte Progenitor Cells Which Is Mediated by the Activation of Both the Ionotropic Glycine Receptor and Na+-Dependent Transporters
Belachew, Shibeshih ULg; Malgrange, Brigitte ULg; Rigo, Jean-Michel et al

in European Journal of Neuroscience (2000), 12(6), 1924-30

Using fluo-3 calcium imaging, we demonstrate that glycine induces an increase in intracellular calcium concentration ([Ca2+]i) in cortical oligodendrocyte progenitor (OP) cells. This effect results from a ... [more ▼]

Using fluo-3 calcium imaging, we demonstrate that glycine induces an increase in intracellular calcium concentration ([Ca2+]i) in cortical oligodendrocyte progenitor (OP) cells. This effect results from a calcium entry through voltage-gated calcium channels (VGCC), as it is observed only in OP cells expressing such channels, and it is abolished either by removal of calcium from the extracellular medium or by application of an L-type VGCC blocker. Glycine-triggered Ca2+ influx in OP cells actually results from an initial depolarization that is the consequence of the activation of both the ionotropic glycine receptor (GlyR) and Na+-dependent transporters, most probably the glycine transporters 1 (GLYT1) and/or 2 (GLYT2) which are colocalized in these cells. Through this GlyR- and transporter-mediated effect on OP intrcellular calcium concentration [Ca2+]i, glycine released by neurons may, as well as other neurotransmitters, serve as a signal between neurons and OP during development. [less ▲]

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See detailEpidermal Growth Factor Upregulates Production of Supernumerary Hair Cells in Neonatal Rat Organ of Corti Explants
Lefèbvre, Philippe ULg; Malgrange, Brigitte ULg; Thiry, Marc ULg 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 detailIdentification of Psf, the Polypyrimidine Tract-Binding Protein-Associated Splicing Factor, as a Developmentally Regulated Neuronal Protein
Chanas-Sacre, Grazyna; Mazy-Servais, Cécile; Wattiez, Ruddy et al

in Journal of Neuroscience Research (1999), 57(1), 62-73

The polypyrimidine tract-binding protein-associated splicing factor (PSF), which plays an essential role in mammalian spliceosomes, has been found to be expressed by differentiating neurons in developing ... [more ▼]

The polypyrimidine tract-binding protein-associated splicing factor (PSF), which plays an essential role in mammalian spliceosomes, has been found to be expressed by differentiating neurons in developing mouse brain. The sequence of a fragment of mouse PSF was found to be remarkably similar to that of human PSF. Both the expression of PSF mRNA in cortex and cerebellum and PSF immunoreactivity in all brain areas were high during embryonic and early postnatal life and almost disappeared in adult tissue, except in the hippocampus and olfactory bulb where various neuronal populations remained PSF-immunopositive. Double-labeling experiments with anti-PSF antibody and anti-neurofilaments or anti-glial fibrillary acidic protein antibodies on sections of cortex, hippocampus, and cerebellum indicate that PSF is expressed by differentiating neurons but not by astrocytic cells. In vitro, mouse PSF was found to be expressed by differentiating cortical and cerebellar neurons. Radial glia or astrocyte nuclei were not immunopositive; however, oligodendrocytes differentiating in vitro were found to express PSF. The restricted expression of PSF suggests that this splicing factor could be involved in the control of neuronal-specific splicing events occurring at particular stages of neuronal differentiation and maturation. [less ▲]

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See detailNeurotransmitter-Mediated Regulation of Cns Myelination: A Review
Belachew, Shibeshih ULg; Rogister, Bernard ULg; Rigo, Jean-Michel et al

in Acta Neurologica Belgica (1999), 99(1), 21-31

In addition to treatments aimed at preventing or limiting damage to myelin and oligodendrocytes, there is a crucial need for repair strategies in human demyelinating disorders. There is increasing ... [more ▼]

In addition to treatments aimed at preventing or limiting damage to myelin and oligodendrocytes, there is a crucial need for repair strategies in human demyelinating disorders. There is increasing evidence that besides growth factors, neurotransmitters can regulate different steps of the oligodendrogliogenesis. The present review on neurotransmitter receptor expression and function in the oligodendrocyte lineage emphasizes the concept that in this lineage cell proliferation and differentiation can be controlled through the modulation of the functional state of channel proteins and receptors, such as the delayed K+ rectifier, the AMPA/kainate, dopamine or muscarinic receptors, and, most likely, others yet to be found. We anticipate that a better understanding of the neurotransmitter-mediated neuronal oligodendroglial communication network opens prospects in the field of central nervous system (CNS) myelin repair, allowing the recruitment of the myelinating machinery that is known to remain present but quiescent in the CNS of multiple sclerosis patients. [less ▲]

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See detailCultured Oligodendrocyte Progenitors Derived from Cerebral Cortex Express a Glycine Receptor Which Is Pharmacologically Distinct from the Neuronal Isoform
Belachew, Shibeshih ULg; Rogister, Bernard ULg; Rigo, Jean-Michel et al

in European Journal of Neuroscience (1998), 10(11), 3556-64

Using the whole-cell patch-clamp technique, we demonstrate glycine-induced currents in oligosphere-derived oligodendrocyte progenitors cultured from newborn rats. Similar inward currents are also ... [more ▼]

Using the whole-cell patch-clamp technique, we demonstrate glycine-induced currents in oligosphere-derived oligodendrocyte progenitors cultured from newborn rats. Similar inward currents are also triggered by beta-alanine and taurine, two established glycine receptor agonists. In our recording conditions, glycine-gated currents in oligodendrocyte progenitors reverse about 0 mV and are reversibly inhibited by the glycine competitive antagonist strychnine, the Cl- channel blocker picrotoxinin and the non-competitive antagonist cyanotriphenylborate. The oligodendrocyte progenitors glycine receptor (GlyR) differs from the corresponding neuronal receptor: [3H]strychnine binding data and the strychnine inhibition curve of glycine-induced currents in oligodendrocyte progenitor cultures suggest the existence of two strychnine binding sites on the oligodendroglial GlyR. Using total RNA isolated from oligodendrocyte progenitors cultures, reverse transcription-polymerase chain reaction analysis of glycine receptor subunit expression shows the presence of alpha2 and beta subunits and immunocytochemical stainings confirm that this GlyR contains an alpha subunit which is not alpha1. The molecular structure of the oligodendroglial GlyR could be either homopentameric alpha2 or heteromeric alpha2beta but in both cases, the sequence of the alpha2 or beta subunits have to be different from the known neuronal sequences in order to explain, respectively, the cyanotriphenylborate (alpha2) and picrotoxinin (beta) sensitivities. This work thus demonstrates that GlyR are expressed by oligodendrocytes obtained not only from spinal cord but also from supraspinal structures. The pharmacological properties and presumably the molecular structure of oligodendroglial GlyR are original. The physiological meaning of the presence of such receptors on developing and mature oligodendrocytes remains unknown. [less ▲]

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See detailExpression of Growth Factors and Their Receptors in the Postnatal Rat Cochlea
Malgrange, Brigitte ULg; Rogister, Bernard ULg; Lefebvre, P. P. 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 detailDevelopmental Regulation of Neuroligand-Induced Responses in Cultured Oligodendroglia
Belachew, Shibeshih ULg; Malgrange, Brigitte ULg; Rigo, Jean-Michel et al

in Neuroreport (1998), 9(6), 973-80

Using whole-cell patch-clamp techniques, we show that oligosphere-derived oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine- and acetylcholine-gated inward currents. When OP ... [more ▼]

Using whole-cell patch-clamp techniques, we show that oligosphere-derived oligodendrocyte progenitor cells (OP) display GABA-, glutamate-, 5-HT-, glycine- and acetylcholine-gated inward currents. When OP differentiate into oligodendrocytes (ODC), the amplitude of peak currents elicited by saturating concentrations of these transmitters decreases except for 5-HT. Intracellular Ca2+ concentration changes induced by microperfusion of glutamate, 5-HT, TRH, met-enkephalin and substance P were monitored using a fluo-3-based calcium imaging system. When OP cells differentiate into ODC, a global decrease of the proportion of responding cells is observed. During type-2 astrocytes commitment, this proportion decreases for 5-HT, TRH- and metenkephalin stimulations whereas it remains constant for substance P and glutamate. These data demonstrate a development regulation of neurotransmitter- and neuropeptide-induced responses within the oligodendroglial lineage. [less ▲]

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See detailDiazepam-Insensitive Gabaa Receptors on Postnatal Spiral Ganglion Neurones in Culture
Malgrange, Brigitte ULg; Rigo, Jean-Michel; Lefebvre, Philippe ULg et al

in Neuroreport (1997), 8(3), 591-6

Using dissociated spiral ganglion cell cultures obtained from 3-day-old rat cochlea, we investigated the response of auditory neurones to gamma-aminobutyric acid (GABA) using patch-clamp techniques. In ... [more ▼]

Using dissociated spiral ganglion cell cultures obtained from 3-day-old rat cochlea, we investigated the response of auditory neurones to gamma-aminobutyric acid (GABA) using patch-clamp techniques. In our recording conditions, GABA elicited inward currents in > 95% of the neurones which reversed around 0 mV. Similar inward currents were measured using isoguvacin, a specific agonist of GABAA receptors. GABA-gated currents were reversibly inhibited by the channel blocker picrotoxin and the GABA competitive antagonist bicuculline. These functional GABAA receptors are characterized by an insensitivity to benzodiazepines and a relatively high sensitivity to beta-carbolines and barbiturates. These results show that the GABAA receptor pharmacological properties of spiral ganglion neurones are close to those of cerebellar granule cells. [less ▲]

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See detailEffect of neuropeptides on cultured postnatal auditory neurons.
Malgrange, Brigitte ULg; Lefebvre, P.P.; Rigo, J.M. et al

Conference (1997)

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See detailBeta-Carbolines Induce Apoptotic Death of Cerebellar Granule Neurones in Culture
Malgrange, Brigitte ULg; Rigo, Jean-Marie ULg; Coucke, Paul et al

in Neuroreport (1996), 7(18), 3041-5

Apart from its role in fast inhibitory transmission, only neurotrophic effects have been reported following activation of the GABAA receptor. Here, we show that n-butyl-beta-carboline-3-carboxylate and n ... [more ▼]

Apart from its role in fast inhibitory transmission, only neurotrophic effects have been reported following activation of the GABAA receptor. Here, we show that n-butyl-beta-carboline-3-carboxylate and n-methyl-beta-carboline-3-carboxamide, which are negative allosteric modulators of the GABAA receptor acting at the benzodiazepine site, are neurotoxic for cerebellar granule neurones in culture. The beta-carboline-induced neuronal death is apoptotic since DNA internucleosomal fragmentation was induced and the neurotoxicity could be prevented by inhibitors of mRNA or protein synthesis. As GABA and benzodiazepine ligands (diazepam and Ro 15-1788) protect cerebellar granule cells against beta-carboline-induced toxicity, these data raise the possibility that the interaction between the beta-carbolines and the GABAA receptor is the triggering event leading to neuronal apoptosis. [less ▲]

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See detailCytokine Production by Human Thymic Epithelial Cells: Control by the Immune Recognition of the Neurohypophysial Self-Antigen
Martens, Henri ULg; Malgrange, Brigitte ULg; Robert, F. et al

in Regulatory Peptides (1996), 67(1), 39-45

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after ... [more ▼]

Oxytocin (OT) has been shown to be the dominant peptide of the neurohypophysial family expressed by thymic epithelial and nurse cells (TEC/TNC) in various species. Thymic OT is not secreted but, after translocation of a hybrid neurophysin/MHC class I protein, is integrated within the plasma membrane of TEC, thus allowing its presentation to pre-T cells. In order to further demonstrate that thymic OT behaves like a membrane antigen, we assessed the effect of mAbs to OT on cytokine productions by cultures enriched in human TEC. 75-85% pure TEC cultures were prepared from human thymic fragments. Using immunofluorescence and confocal microscopy, ir-OT, ir-interleukin-1 beta (IL-1 beta), ir-interleukin-6 (IL-6) and ir-leukemia inhibitory factor (LIF) could be detected in these TEC cultures. ir-OT was restricted to TEC, while some ir-IL-6 and ir-LIF were also seen in occasional fibroblasts. In basal conditions, ir-IL-6 and ir-LIF (but not ir-OT and ir-IL-1 beta) were detected in the supernatants of human TEC cultures. MAbs to OT induced a marked increase of ir-IL-6 and ir-LIF secretion in TEC cultures. No significant effect was observed using mAbs against vasopressin, mouse immunoglobulins, or control ascitic fluid controls. These data show that OT is fully processed and recognized by specific mAbs at the outer surface of TEC plasma membrane. They further support that thymic OT behaves as the self-antigen of the neurohypophysial family. [less ▲]

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See detailNt-3 Has a Tropic Effect on Process Outgrowth by Postnatal Auditory Neurones in Vitro
Malgrange, Brigitte ULg; Lefebvre, P. P.; Martin, Didier ULg 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 detailNeurotrophic Factors: Past and Future
Moonen, Gustave ULg; Malgrange, Brigitte ULg; Rigo, Jean Michel et al

in Acta Neurologica Belgica (1996), 96(3), 203-18

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