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Biomedical subjects

G Moonen

Publications and source records attributed to G Moonen.

At least 91 records · Page 5Linked to original sources
PubMed1993

Neuron-specific enolase as a marker of in vitro neuronal damage. Part I: Assessment of neuron-specific enolase as a quantitative and specific marker of neuronal damage.

Enolase in cerebrospinal fluid is a sensitive marker for many types of neurological injuries including head injury and ischemia. We assessed neuron-specific enolase (NSE) as a quantitative and specific biochemical marker of neuronal damage in an experimental model of kainate neurotoxicity. Rat hippocampal cultures were treated with various concentrations of kainate. NSE release into the culture medium was compared with neuronal death estimated either by direct cell counting or by lactate dehydrogenase (LDH) release, largely used to quantify neuronal injury. A dose-response relationship was observed between kainate concentration and the amount of NSE released (r = -0.69; p < 0.05) as well as a significant correlation between NSE release and neuronal death (r = 0.64; p < 0.05). Likewise, a significant correlation was found between LDH and NSE release (r = 0.85; p < 0.05). The specificity of NSE as an indicator of neuronal death was demonstrated using immunocyto-chemistry labeling and measurement of NSE release by pure astrocyte cultures. We concluded that NSE is a reliable, quantitative, and specific marker of neuronal injury.

Animals↗
PubMed1993

Neuron-specific enolase as a marker of in vitro neuronal damage. Part II: Investigation of the astrocyte protective effect against kainate-induced neurotoxicity.

The protective effect of astrocytes on hippocampal neurons against kainate-induced toxicity was investigated using neuron-specific enolase as an indicator of neuronal death. Astrocyte-rich and astrocyte-poor mixed rat hippocampal cultures were submitted to various concentrations of kainate. At each kainate concentration, the amount of NSE released by neurons was significantly greater in astrocyte-poor than in astrocyte-rich cultures (p < 0.05). This protective effect was not observed when neuronal survival was tested on astrocyte-poor cultures in astrocyte-conditioned culture medium with or without 10(-4) M kainate. In conclusion, astrocytes significantly attenuate kainate toxicity on hippocampal neurons, and this effect is not mediated by a diffusible factor.

Animals↗
PubMed1993

Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

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.

Animals↗
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↗