References of "Moonen, Gustave"
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See detailSpontaneous longitudinally orientated axonal regeneration is associated with the Schwann cell framework within the lesion site following spinal cord compression injury of the rat.
Brook, G. A.; Plate, D.; Franzen, Rachelle ULg et al

in Journal of Neuroscience Research (1998), 53(1), 51-65

Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis ... [more ▼]

Spontaneous cellular reorganisation at the lesion site has been investigated following massive spinal cord compression injury in adult rats. By 2 days post operation (p.o.), haemorrhagic necrosis, widespread axonal degeneration, and infiltration by polymorphnuclear granulocytes and OX42-positive macrophages were observed in the lesion site. By 7 days p.o., low affinity nerve growth factor receptor-positive Schwann cells, from activated spinal roots, were identified as they migrated far into the lesion. Between 7 and 14 days p.o., the overlapping processes of Schwann cells within the macrophage-filled lesion formed a glial framework which was associated with extensive longitudinally orientated ingrowth by many neurofilament-positive axons. Relatively few of these axons were calcitonin gene-related peptide (CGRP)-, substance P (SP)-, or serotonin (5HT)-positive; however, many were glycinergic or gamma aminobutyric acid (GABA)ergic. At 21 and 28 days p.o. (the longest survival times studied), a reduced but still substantial amount of orientated Schwann cells and axons could be detected at distances of up to 5 mm within the lesion. Glial fibrillary acidic protein (GFAP) immunoreactivity demonstrated the slow formation of astrocytic scarring which only became apparent at the lesion interface between 21 and 28 days p.o. The current data suggest the possibility of developing future therapeutic strategies designed to maintain or even enhance these spontaneous and orientated regenerative events. [less ▲]

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See detailSpontaneous axonal regeneration into the lesioned site following closed contusion injury to the adult rat spinal cord.
Brook, G.; Plate, D.; Schmitt, A. B. et al

Conference (1997, October)

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See detailSpinal injury and spinal cord injury
Martin, Didier ULg; Moonen, Gustave ULg

Conference (1997, September 12)

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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, Philippe ULg; Rigo, J.M. et al

Conference (1997)

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See detailJean Marquet Award. Regeneration of the neurosensory structures in the mammalian inner ear.
Lefèbvre, Philippe ULg; Malgrange, Brigitte ULg; Van de Water, T. et al

in Acta Oto-Rhino-Laryngologica Belgica (1997), 51(1), 1-10

Regeneration of the neurosensory structures in the mammalian inner ear. Motivated by the absence of treatment of neurosensory deafness apt to restore auditory function or alter the course of progressive ... [more ▼]

Regeneration of the neurosensory structures in the mammalian inner ear. Motivated by the absence of treatment of neurosensory deafness apt to restore auditory function or alter the course of progressive hearing loss, we developed two different experimental strategies to approach these diseases: one is otoprotection, designed to prevent further degradation of auditory function; the other is regeneration which is defined as the replacement of hair cells in the deaf ear and their reconnection to the central nervous system through primary auditory neurons. In this paper, we summarize our data on the regeneration of auditory neurons and hair cells. Neuronal maintenance and regeneration was studied through an initial investigation of growth factors during inner development. Once the effect of various neurotrophic molecules was determined, the factors were tested on mature auditory neurons in vitro and in vivo. The hair cell regeneration was investigated on the basis of a concept derived from comparative physiology and from the study of the development of the inner ear. We showed that in young rats it is possible to induce the regeneration/repair of hair cells in the organ of Corti in cultures using retinoic acid and transforming growth factor alpha. The clinical prospects of these findings of inner ear regeneration are discussed. [less ▲]

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See detailLabelling of an intermediate-filament-associated protein in cerebellar radial glial cells with the RC2 antibody
Leprince, P; Chanas-Sacre, G; Lewin, M et al

Poster (1997)

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See detailMicroexplant cultures of the cerebellum
Rogister, Bernard ULg; Moonen, Gustave ULg

in Fedoroff, Serguei; Richardson, Anne (Eds.) Protocols for Neural Cell Culture (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 detailProtein Kinase- and Staurosporine-Dependent Induction of Neurite Outgrowth and Plasminogen Activator Activity in Pc12 Cells
Leprince, Pierre ULg; Bonvoisin, Catherine ULg; Rogister, Bernard ULg et al

in Biochemical Pharmacology (1996), 52(9), 1399-405

We analysed how interactions between protein kinase-dependent intracellular signalling pathways were implicated in the control of the production of tissue-type plasminogen activator (tPA) and the ... [more ▼]

We analysed how interactions between protein kinase-dependent intracellular signalling pathways were implicated in the control of the production of tissue-type plasminogen activator (tPA) and the generation of neurite outgrowth by PC12 cells. To that aim, cells were treated with agents that interact with the trk receptor and with protein kinases A and C. Nerve growth factor induced only the formation of large neurites. The release of the protease and the production of short neurite outgrowth were found to be protein-kinase-A-dependent events that could be enhanced by simultaneous activation of protein kinase C with phorbol ester. At high concentration, staurosporine, a nonselective inhibitor of protein kinases, induced the production of short neurites and mimicked the protein-kinase-A-dependent effect on tPA release. Such a response was not observed with K-252a, an analogue of staurosporine devoid of neurite-outgrowth-promoting activity. The responses to protein kinase A stimulation and the addition of staurosporine, although similar, seemed to occur through an activation of distinct, yet interacting, signalling pathways. In conclusion, tPA release and large neurite outgrowth from PC12 cells are controlled by parallel, albeit interacting, pathways, suggesting that these two potentially antagonistic events in PC12 cell differentiation can be modulated in a concerted way or independently of each other, depending on the activity of several protein kinases. [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, Philippe ULg; 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 detailEffects of Schwann Cell Transplantation in a Contusion Model of Rat Spinal Cord Injury
Martin, Didier ULg; Robe, Pierre ULg; Franzen, Rachelle ULg et al

in Journal of Neuroscience Research (1996), 45(5), 588-597

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ... [more ▼]

Cultured Schwann cells were transplanted at various delays into a spinal cord contusion injury performed at low thoracic level in adult female rats. The Schwann cells were purified from the dorsal root ganglia of adult syngeneic animals. the transplants were well tolerated, and the transplanted Schwann cells invaded the injured spinal cord. As quantified using video image analysis, the survival and growth of the transplanted cells were poor when the grafting procedure was performed 3-4 days after injury and very good when performed immediately or 10 days after injury, in which cases post-traumatic micro- and macrocavitation were strongly reduced. In animals grafted immediately after injury but not in animals grafted after 10 days, post-traumatic astrogliosis was much reduced. The Schwann cells transplanted area was invaded by numerous regenerating axons, the vast majority of which were, based on the neurotransmitter (CGRP and SP) profile, originating from dorsal root ganglion. No regeneration of the corticospinal tract as assessed after anterograde tracing or of descending aminergic fibers could be demonstrated. [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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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 (The) (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 ULg 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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