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Biomedical subjects

G Moonen

Publications and source records attributed to G Moonen.

At least 19 recordsLinked to original sources
PubMed1992

Experimental acute traumatic injury of the adult rat spinal cord by a subdural inflatable balloon: methodology, behavioral analysis, and histopathology.

We describe an experimental model to produce closed traumatic injuries to the spinal cord of adult rats. This model uses an inflatable balloon that is introduced in the dorsal subdural space and moved to a location rostral to the laminectomy site. The spinal cord trauma can be graded by varying either the duration of compression or the volume of saline used to inflate the balloon. The locomotor deficit of animals with various degrees of injury has been assessed at increasing delays after trauma. The parameters generating transient or definitive deficits of varying intensity were defined. Some injured animals underwent nuclear magnetic resonance imaging. Detailed histopathological studies demonstrated that the extent of the spinal lesion was significantly correlated with the physical parameters of compression and with the severity of the behavioral deficit.

Animals↗
PubMed1992

MRI-pathological correlations in acute traumatic central cord syndrome: case report.

Ante- and post-mortem MRI and detailed pathological examination were performed in a patient with a typical acute traumatic central cord syndrome (ATCCS) after a minor hyperextension injury to the neck who died 60 h later from heart failure. T2-weighted MRI showed a central hyperintense area at C3-4. There were disc protrusions, but no vertebral fracture or displacement. Histopathology disclosed severe axonal swelling and oedema in the dorsolateral fasciculi and, to a lesser degree, in the dorsal columns. In addition, an area of recent necrosis was found in the right anterior horn at C4-5. These findings suggest that the pathological hallmark of typical ATCCS is mechanical axonal disruption at a segmental level, but that more severe trauma may be accompanied by tissue destruction.

Axons↗
PubMed1992

Peripheral and central target-derived trophic factor(s) effects on auditory neurons.

In the developing inner ear, a naturally occurring programmed cell death of cochleovestibular ganglion (CVG) neurons as well as peripheral and central target-derived trophic effects on survival of embryonic CVG neurons are known. To further analyze these target derived trophic interactions, spiral ganglion explants obtained from 5 day postpartum (P5) rat pups were cultured with an intact organ of Corti and in the absence of Corti's organ. Both neuronal survival and neurite extension were influenced by the presence of this peripheral target tissue. Local destruction of Corti's organ caused both neuritic retraction and neuronal cell death to occur in a corresponding portion of the spiral ganglion. This peripheral target-derived neurotrophic effect may be mediated by a diffusible factor(s) since organ of Corti conditioned medium also had a neurotrophic effect on the survival of auditory neurons in cell cultures of dissociated spiral ganglia from P5 rat pups. A component of central target tissue, i.e. astrocytes, was also shown to release a diffusible factor(s) that supported the survival of dissociated P5 rat spiral ganglion neurons. The neurotrophic effects on the in vitro survival of spiral ganglion neurons by both of these conditioned medium factors were concentration dependent.

Animals↗
PubMed1992

Unilateral facial pain as the first symptom of lung cancer: are there diagnostic clues?

We describe three patients with unilateral facial pain due to non-metastatic lung cancer and review 11 published cases. Pain, most frequently located on the right side and around the ear, as well as digital clubbing can be clues to an early diagnosis. Compression of the vagus nerve by the tumour or by mediastinal adenopathy is most likely responsible for the facial pain and could play a role in pulmonary osteoarthropathy.

Adult↗
PubMed1992

Nerve growth factor stimulates neurite regeneration but not survival of adult auditory neurons in vitro.

Injury to either the peripheral or central nervous system results in the accumulation of growth factors at the wound site. Some of these growth factors have been shown to participate in the neural repair process. Adult auditory neurons grown in dissociated spiral ganglion cell cultures are injured (i.e. bilateral axotomy) as a result of the initial preparation of these cultures. Therefore, cell cultures of dissociated spiral ganglia provide a model for the study of repair processes of adult auditory neurons (e.g. effects of exogenous growth factors on the process of neuritogenesis by injured neurons). Auditory neurons do not survive in these dissociated ganglion cell cultures when only exogenous NGF is added to the defined culture medium. Previous work has identified substrate bound basic fibroblast growth factor (bFGF) as a survival factor for adult auditory neurons in vitro. Auditory neurons cultured on substrate bound bFGF also do not show increased survival in response to the addition of increasing concentrations of nerve growth factor (NGF) to the defined medium. This is in sharp contrast to the pronounced neurite outgrowth-promoting effects (concentration dependent) observed when exogenous NGF is added to adult auditory neurons cultured on substrate bound bFGF. We propose that several neuronotrophic factors (e.g. TGFB1, bFGF, NGF and other neurotrophins) are active in the spiral ganglions' response to injury. Several of these growth factors (i.e. bFGF, NGF) act in cooperation to promote the regeneration or repair of severed or traumatized neuritic processes.

Animals↗
PubMed1992

TGF beta 1 expression is initiated in adult auditory neurons by sectioning of the auditory nerve.

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.

Animals↗
PubMed1991

Growth factor interactions in cultures of dissociated adult acoustic ganglia: neuronotrophic effects.

Auditory neurons cultured from adult rat acoustic ganglia require for survival either a substrate bound factor(s) present in astrocyte conditioned medium or substrate bound basic fibroblast growth factor (bFGF). Nerve growth factor (NGF) is not a survival factor for these neurons in vitro, but when used in combination with substrate bound bFGF, NGF does vigorously stimulate a neuritogenesis response by these neurons. Transforming growth factor beta (TGF beta 1) enhances the survival effect that bFGF has on these adult auditory neurons but does not by itself promote their survival in dissociated acoustic ganglion cultures. We propose that there may be complex interactions and synergy exerted by these growth factors (i.e. bFGF, NGF, TGF beta 1) during injury to the inner ear.

Animals↗
PubMed1991

Kainate and NMDA toxicity for cultured developing and adult rat spiral ganglion neurons: further evidence for a glutamatergic excitatory neurotransmission at the inner hair cell synapse.

In the inner ear, the excitatory amino acid glutamate is a proposed neurotransmitter acting at the synapse between hair cells and afferent auditory neurons. Using cultures of 5-day-old rat auditory neurons, we show that the afferent auditory neuronal population can be divided, on the basis of its sensitivity to the neuronotoxic effect of glutamate and its analogs, in at least 3 subpopulations, one responding to N-methyl-D-aspartate (NMDA), one responding to kainate and a third minor one unresponsive to NMDA, kainic acid and glutamate. No toxic effect of quisqualate is observed. The use of specific antagonists (kynurenate and 2-amino-5-phosphonovalerate (DAP-5) demonstrates the specificity of the receptors to the excitatory amino acids on the afferent auditory neurons. Afferent auditory neurons from adult rats can also be cultured and in these preparations only the large neurons are sensitive to glutamate, kainate and NMDA while the small neurons are not responsive, suggesting that a glutamatergic neurotransmission occurs only at this synapse between the inner hair cells and the large radial afferent auditory neurons. We also show that, in vitro, the organ of Corti releases, in response to an increased potassium concentration and in the presence of calcium, a toxic activity for the afferent auditory neurons that is antagonized by kynurenate and DAP-5. Pathophysiological implications are discussed.

2-Amino-5-phosphonovalerate↗
PubMed1991

Grafts of syngenic cultured, adult dorsal root ganglion-derived Schwann cells to the injured spinal cord of adult rats: preliminary morphological studies.

Highly enriched cultures of Schwann cells were obtained from adult rat dorsal root ganglia and implanted (5 x 10(5) -9 x 10(5) cells) in the spinal cord of syngenic adult rats at the site of an acute compression lesion produced by a subdural inflatable microballoon. These autografts survived and invaded the host tissue, reducing central cavitation and astrocytic gliosis. They dramatically promoted ingrowth of axons, the majority of which appeared to come from the dorsal roots as judged by their neuropeptide content. Invasion of the transplants by descending, e.g. aminergic fibers, was negligible at survival times of up to 4 months. Nonetheless, autologous Schwann cells, which are readily available in the host, represent a promising material for grafts into the injured spinal cord.

Animals↗
PubMed1991

TGFSS1 modulates bFGF receptor message expression in cultured adult auditory neurons.

Basic fibroblast growth factor (bFGF) has been shown to have neuronotrophic effects on cultured neurons. Transforming growth factor beta (TGFss1) has been implicated in the modulation of cellular receptors for bFGF in several cell types. In this study, we show that TGFss1 is expressed in cultured adult mouse auditory neurons in response to explanation injury and acts in an autocrine fashion to increase the level of expression of bFGF receptors message in these same neurons. Based on these in-vitro results, we propose that these trophic factors (i.e. TGFss1 and bFGF) play a significant role in the response to injury by the mature auditory system.

Animals↗
PubMed1991

Modulation of proteolytic activity during neuritogenesis in the PC12 nerve cell: differential control of plasminogen activator and plasminogen activator inhibitor activities by nerve growth factor and dibutyryl-cyclic AMP.

Extracellular proteolysis is considered to be required during neuritic outgrowth to control the adhesiveness between the growing neurite membrane and extracellular matrix proteins. In this work, PC12 nerve cells were used to study the modulation of proteolytic activity during neuronal differentiation. PC12 cells were found to contain and release a 70-75-kDa tissue-type plasminogen activator (tPA) and a much less abundant 48-kDa urokinase-type plasminogen activator. A plasminogen activator inhibitor (PAI) activity with molecular sizes of 54 and 58 kDa was also detected in PC12 cell conditioned medium and formed high-molecular-mass complexes with released tPA. Release of PAI activity was dependent on treatment with nerve growth factor (NGF), whereas tPA synthesis and release were under control of a cyclic AMP-dependent mechanism and increased on treatment with dibutyryl-cyclic AMP [(But)2cAMP] or cholera toxin. Simultaneous treatment with NGF and (But)2cAMP resulted in increases of both tPA and PAI release and enhancement of tPA-PAI complex formation. The resulting plasminogen activator activity in conditioned medium was high in (But)2cAMP-treated cultures with short neuritic outgrowth but remained low in NGF- or NGF plus (But)2cAMP-treated cultures, where neurite extension was, respectively, large and very large. These results suggest that excess proteolytic activity may be detrimental to neuritic outgrowth and that not only PAI release but also tPA-PAI complex formation is associated with production of large and stable neuritic outgrowth. This can be understood as an involvement of PAI in the protection against neurite-destabilizing proteolytic activity.

Adrenal Gland Neoplasms↗
PubMed1991

Temporal pattern of nerve growth factor (NGF) binding in vivo and the in vitro effects of NGF on cultures of developing auditory and vestibular neurons.

NGF binding patterns reflect the presence of receptors for this growth factor. High specific binding of 125I 2.5 S-NGF was observed for the 11 gestation day (gd) statoacoustic ganglion (SAG) with lower levels recorded for both 14 gd acoustic ganglion (AG) and vestibular ganglion (VG) samples. Fourteen day AG cells were more than twice as active for binding NGF when compared to VG samples of the same gestational age. Both whole ganglion explants and dissociated cell cultures were grown in chemically defined medium for short term culture to assay changes in neurite outgrowth and survival of neurons in response to the addition of exogenous 2.5 S-NGF. The most vigorous neurite outgrowth and neuronal survival responses were produced by 11 gd SAG samples treated with NGF. Acoustic ganglion specimens of both 11 gd and 14 gd embryos were much more responsive to the neurotrophic effects of NGF when compared to the responses of their VG counterparts. There was a correlation between NGF binding ability and in vitro responsiveness to exogenous NGF. We hypothesize based on the results of this study that NGF (and/or a member of the NGF family of growth factors) is involved in the control of developmentally regulated neuronal cell death of SAG neurons and may play a role in the innervation of developing inner ear sensory structures.

Animals↗
PubMed1990

Potassium-induced release of an endogenous toxic activity for outer hair cells and auditory neurons in the cochlea: a new pathophysiological mechanism in Menière's disease?

In Menière's disease, the increase of extracellular potassium concentration in the perilymph is thought to play a key role in determining the progressive loss of cochlear hair cells. In this paper, we describe a serum-free culture preparation of hair cells from 5 day-old rat and report the release by the cochlea, in response to an increase of extracellular potassium concentration, of a cytotoxic activity active on hair cells and auditory neurons. The toxic activity is associated with low molecular weight (less than 10,000 Dalton) molecule(s) as revealed by ultrafiltration. Morphological studies performed on the organ of Corti incubated during 24 h in the presence of the cochlea-derived toxic activity (CTA), show that this factor is toxic for hair cells and not for supporting or surrounding cells. The release of CTA occurs both in the spiral ganglion and in the organ of Corti. We suggest that this cochlea-derived toxic activity may play an important role in the pathophysiology of the hearing loss that occurs during the progression of Menière's disease.

Animals↗
PubMed1990

Neuronotrophic effect of developing otic vesicle on cochleo-vestibular neurons: evidence for nerve growth factor involvement.

In the developing inner ear, the existence of a neuronal death and of a peripheral target-derived trophic effect on cochleovestibular neurons has been documented. Using cultures of rat cochleovestibular neurons, we show that the E12 otic vesicle releases a factor promoting the survival and the neuritogenesis of these neurons, and that this effect is mimicked by NGF. The effect of the optic vesicle conditioned medium (OVCM) on cochleovestibular neurons is suppressed by anti-NGF antibodies. OVCM is neuronotrophic for NGF-sensitive sympathetic neurons, an effect that is also suppressed by anti-NGF antibodies, further demonstrating the presence of biologically active nerve growth factor.

Adrenergic Fibers↗
PubMed1990

Enhanced release of plasminogen activator inhibitor(s) but not of plasminogen activators by cultured rat glial cells treated with interleukin-1.

Astroglial cells are known to proliferate during development of the nervous system, as well as during post-traumatic gliosis. We have previously shown that the proliferation of cultured astrocytes can be stimulated by the urokinase-type (uPA) of plasminogen activator (PA) and that astrocytes are able to release such uPA upon stimulation with basic fibroblast growth factor, which is known to act as a mitogen for these cells. Here we report studies on the effects of human interleukin-1 (IL-1) on the release of PA activity by cultured newborn rat astroglial cells. Whereas there is controversy in the literature as to whether IL-1 stimulates multiplication of astroglial cells, we failed to observe such an effect in our system. We did observe, however, a dose-dependent decrease in PA activity in the supernatant of the IL-1 treated cultures. Further analysis revealed that this apparent decrease in PA release was in fact due to an increased release of plasminogen activator inhibitor (PAI). A similar IL-1 induced increase in PAI release was also found to occur in cultures of transformed astrocytes (human glioma LN18) and in cultured Schwann cells, but not in cultures of neurons or neuronal tumour cells. Since protease inhibitors are known to possess neuritogenic properties, our results suggest that IL-1, by its capacity to induce PAI, may promote neuritogenesis.

Adrenal Gland Neoplasms↗
PubMed1990

Cultured neurons release an inhibitor of astroglia proliferation (astrostatine).

Using in vitro techniques, we looked for a possible downregulation of rat astroglia proliferation by neuronal cells. We demonstrate that medium conditioned by 7-day-old rat cerebellar granule neurons or by 16-day-old rat embryo hippocampal neurons strongly inhibits the proliferation of cultured astroglial cells. Two neuronal cell lines, the PC12 rat pheocromocytoma and the neuro 2A (N2A) murine neuroblastoma also release such an activity. This release in N2A-conditioned medium (CM) occurs when the cells are at high density and show a low proliferation rate. This activity is present in media conditioned by neuronal cells, but not in media conditioned by normal astrocytes, by two glioma cell lines, or by one fibroblastic cell line. This proliferation inhibitor addresses normal astrocytes: the proliferation of two glioma cell lines, of a fibroblastic cell line, and of the two neuronal cell lines (PC12, N2A) is not inhibited by N2A CM. Moreover, this activity is directed against type 1 astrocytes, but not against type 2. Using three different assays, we demonstrate that DNA synthesis by astroglial cells is inhibited. N2A CM has no cytotoxic effect on astrocytes and does not modify their overall protein synthesis. Using affinity and gel filtration chromatography, we show that this activity is associated with a protein whose molecular weight ranges between 15 and 20 kDa. The possible relationship between this N2A cell-derived astroglia proliferation inhibitor and other types of potential glial proliferation inhibitors has been investigated. A brain glycoprotein immunologically related to epidermal growth factor receptor (EGFR) was reported to inhibit astroglial cell proliferation in vitro. Using polyclonal and monoclonal antibodies against EGFR, we were unable to immunoprecipitate the astrocyte proliferation inhibitor in N2A CM or to demonstrate by immunoblotting the presence of an EGFR-like immunoreactivity in the N2A CM or in the active chromatographic fractions of N2A CM. Transforming growth factor beta (TGF beta) is a well-known modulator of the proliferation of various cell types and was shown to be present in N2A CM. Using a polyclonal anti-TGF beta antibody that recognizes TGF beta on Western blots of N2A CM, we were unable to immunoprecipitate the astrocyte proliferation inhibitor of N2A CM. It seems thus far that the neuronal astroglia proliferation inhibitor is a new protein for which we propose the name astrostatine.

Animals↗
PubMed1990

An in vivo model of varicella-zoster virus latent infection of dorsal root ganglia.

We describe here the first in vivo model of varicella-zoster virus (VZV) latent infection in the adult rat peripheral nervous system. Infected Mewo cells were injected subcutaneously along the spine of healthy adult rats. No clinical sign of infection was observed even 9 months after inoculation. Humoral immune response to VZV was detected in all infected animals throughout the study (9 months). The presence of viral material in dissociated and cultured dorsal root ganglia (DRG) from inoculated animals was studied by immunoperoxidase and in situ hybridization. When DRGs from infected animals were plated in culture from 1 month and up to 9 months after inoculation, viral nucleic acids and proteins were detected in neurons. Furthermore, trypsinization and subcultivation of infected neurons in culture is needed to reactivate infectious virus at least in some of the neurons. This model provides a useful tool for studying 1) the molecular mechanisms leading to an in vivo latency, 2) the role of the immune system, in particular cellular immunity, on the establishment, maintenance, and reactivation of latency, 3) the neurotropism of mutant viruses, and 4) the effects of antiviral agents.

Animals↗