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Biomedical subjects

G Moonen

Publications and source records attributed to G Moonen.

At least 73 records · Page 4Linked to original sources
PubMed1996

Neurotrophic effects of BDNF and CNTF, alone and in combination, on postnatal day 5 rat acoustic ganglion neurons.

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.

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PubMed1996

Neurotrophic factors as pharmacological agents for the treatment of injured auditory neurons.

Mature auditory neurons degenerate in response to a loss of target-derived trophic factors. Neurotrophic factors influence the health and viability of auditory neurons. This suggests that neurotrophic factors can be used as therapeutic agents to prevent neuronal cell death and to initiate repair of damaged neuronal processes in the injured auditory system. Both in vitro and in vivo experiments have been performed to determine which of the vast array of neurotrophic factors affect mature auditory neurons and how they can be delivered to the sites of injury within the auditory system. Neurotrophin 3 was found to be a major survival factor for auditory neurons. Brain-derived neurotrophic factor is a minor survival factor for auditory neurons and nerve growth factor, although not promoting survival, does elicit the repair of neuronal processes. Fibroblast growth factor 2, transforming growth factor beta 1 and ciliary neurotrophic factor function as injury-response factors in the auditory system. Combination of different classes of growth factors has an additive effect on neuronal survival. Growth factors may be able to be delivered to sites of injury within the cochlea by either direct perfusion or gene therapy (e.g. a defective virus expressing a growth factor gene).

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PubMed1996

Effect of neurotrophic factors on the inner ear: clinical implications.

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.

Animals↗
PubMed1996

The role of the neurotrophins in maturation and maintenance of postnatal auditory innervation.

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.

Animals↗
PubMed1995

NT-3 combined with CNTF promotes survival of neurons in modiolus-spiral ganglion explants.

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.

Animals↗
PubMed1995

Preparation of a macroporous biodegradable polylactide implant for neuronal transplantation.

This article reports the production of a surgical implant meeting several specific requirements such as biocompatibility, biodegradability, macroporosity, and flexibility. Porosity was controlled by an original method consisting of the aggregation of calibrated poly-D,L-lactide microparticles. The size of the interstices between the aggregated microspheres was in a direct relationship to the microsphere diameter. A first approach was based on coating the microspheres with poly(vinyl alcohol) followed by chemically crosslinking the coating layers that were in mutual contact. This method was disregarded because of the acute cytotoxicity of glutaraldehyde used as the crosslinking agent, the absence of macroporosity, and the complete lack of flexibility. A physical technique of aggregation was then tested, which relied on the plasticization of poly-D,L-lactide microspheres with triethylcitrate to the point where microspheres strongly adhered to each other when they were in contact. This method has proved to be straightforward and definitely superior to the chemical approach, particularly with respect to cytotoxicity, control of macroporosity, and flexibility. A polymer support was thus successfully which was biodegradable, macroporous( interconnected pores of 10-100 microns in diameter), and flexible. This potential medical device is presently being used for neuronal transplantation in the central nervous system.

Animals↗
PubMed1994

Astroglia-released factor shows similar effects as benzodiazepine inverse agonists.

Media conditioned by cultured neonatal cerebral cortex microexplants (CCM) or astrocytes (ACM) contain low molecular weight (< 1,000 Da) substance(s) which inhibits the gamma aminobutyric acid (GABA)-induced inward current recorded in cerebellar granule cells and hippocampal neurons in culture using the whole-cell patch-clamp technique. This effect is specific for CCM and ACM, as medium conditioned by PC12 cells (PC12CM) does not affect the GABA response of these cells. It is also specific for GABA-induced currents because glutamate-induced currents do not change either in amplitude or in shape in the presence of CCM or ACM. The inhibitory effect on the GABA response in cerebellar granule cells of both ACM and CCM could be suppressed by flumazenil, a specific benzodiazepine (BZD) antagonist and could be mimicked by two BZD inverse agonists. These data thus demonstrate the presence of a BZD inverse agonist-like activity in CCM and ACM. This effect of ACM on different neuronal cell types was heterogenous since no detectable effect could be observed on the GABA-induced current in GABA-responsive dorsal root ganglion (DRG) neurons, presumably reflecting a functional heterogeneity of the GABAA receptors present in these different neuronal subsets. By the release of such an endogenous BZD inverse agonist-like activity, glia cells could possibly modulate GABAA receptor-mediated responses.

Animals↗
PubMed1994

Neurotrophins affect survival and neuritogenesis by adult injured auditory neurons in vitro.

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).

Animals↗
PubMed1994

Radiation-induced myelopathy and vertebral necrosis.

Radiation-induced myelopathy is often a diagnosis of exclusion. In addition to the classic criteria needed to support the diagnosis, the presence of another radiation-induced lesion, such as aseptic vertebral necrosis, is useful to confirm the cause of the spinal cord lesion.

Aged↗
PubMed1994

Image analysis of neuritic regeneration by adult rat dorsal root ganglion neurons in culture: quantification of the neurotoxicity of anticancer agents and of its prevention by nerve growth factor or basic fibroblast growth factor but not brain-derived neurotrophic factor or neurotrophin-3.

Peripheral neuropathies are a common side effect of chemotherapeutic agents, particularly antineoplastic drugs such as taxol, cisplatin, or vinca-alkaloids (vincristine, vinblastine, vindesine). Using dissociated cultures of adult rat dorsal root ganglion (DRG) neurons and video image analysis after neurofilament immunostaining, we have designed a system that allows: (i) rapid screening of potential neurotoxic agents, with the establishment of dose-response curves and the calculation of IC50; (ii) quantification of neurotrophic effects; and (iii) demonstration of neuroprotection by trophic factors. In particular, we show that nerve growth factor (NGF) and basic fibroblast growth factor (bFGF) stimulate in vitro neuritic regeneration by adult rat DRG neurons, while brain-derived neurotrophic factor and neurotrophin-3 lack such effects. Furthermore, 24 h of pretreatment by NGF or bFGF drastically decreases the neurotoxic effect of vincristine and cisplatin.

Animals↗
PubMed1994

Propofol protects cultured rat hippocampal neurons against N-methyl-D-aspartate receptor-mediated glutamate toxicity.

The effect of propofol on the toxicity induced by glutamate (GLU), N-methyl-D-aspartate (NMDA), kainate (KA), and amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) was investigated on cultured fetal rat hippocampal neurons. The degree of neuronal injury was quantified by measuring the release of the neuron-specific enolase (NSE) into the culture media. The toxicity induced by brief exposure to GLU (10(-4) M) or to NMDA (10(-4) M) was significantly reduced by propofol, whereas that elicited by KA, AMPA (10(-4) M), or long GLU exposure was unaffected. In conclusion, high concentrations of propofol significantly attenuate NMDA receptor-mediated glutamate neurotoxicity in vitro. Further studies are needed to confirm this beneficial effect in vivo and to evaluate propofol as a neuroprotective anesthetic agent in pathologies involving glutamate release and NMDA-mediated toxicity.

Animals↗
PubMed1993

Retinoic acid stimulates regeneration of mammalian auditory hair cells.

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.

Animals↗
PubMed1993

Plasticity of developing and adult dorsal root ganglion neurons as revealed in vitro.

We review recent data on the plasticity of dorsal root ganglion (DRG) neurons as revealed during cultivation in vitro. Some experiments on cultured developing DRG neurons and on adult DRG neurons in vivo are also mentioned. Cultured developing and adult DRG neurons can be switched from an apolar to a multipolar phenotype by fetal calf serum or fibronectin. The effect is concentration dependent and occurs through an early modification of cell-substratum interaction. Adult DRG neurons synthesize and release within hours after injury TGF beta-1, which is a mitogen and a differentiation factor for Schwann cells. Finally, adult DRG neurons express in vitro neurotransmitters that are not expressed in vivo. This neurotransmitter plasticity can be modulated in vitro by some growth factors and in vivo by distal or proximal axotomy.

Animals↗
PubMed1993

Syngeneic grafting of adult rat DRG-derived Schwann cells to the injured spinal cord.

A subdural inflatable micro-balloon was used to induce closed traumatic contusion to adult rat spinal cord. This spinal cord injury model was associated with reproducible and graded neurological deficits and histopathological alterations. At various delays after injury, transplantations of syngeneic adult cultured dorsal root ganglion-derived Schwann cells were performed into the spinal cord lesion. The transplants were well integrated and reduced the microcystic posttraumatic cavitation as well as the gliosis. Schwann cells transplants were invaded by numerous regenerating neurites most of which, based upon their neurotransmitter contents, seem to originate from the dorsal root ganglion.

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