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Biomedical subjects

B Renaud

Publications and source records attributed to B Renaud.

At least 19 recordsLinked to original sources
PubMed2005

Variations in extracellular levels of dopamine, noradrenaline, glutamate, and aspartate across the sleep--wake cycle in the medial prefrontal cortex and nucleus accumbens of freely moving rats.

We used intracerebral microdialysis coupled with electrophysiologic recordings to determine relative changes in the concentrations of several neurotransmitters in the medial prefrontal cortex and nucleus accumbens of freely moving rats during waking, slow-wave sleep, and rapid eye movement (REM) sleep. The concentrations of noradrenaline, dopamine, glutamate, and aspartate in 2-min dialysate samples were analyzed by capillary electrophoresis combined with laser-induced fluorescence detection. Changes in glutamate and aspartate concentrations were found only in the nucleus accumbens, in which a decrease was obtained during both slow-wave sleep and REM sleep compared to waking. A progressive reduction in the release of noradrenaline was observed from waking to REM sleep in both structures. In contrast, dopamine concentrations were higher during waking and REM sleep compared to that during slow-wave sleep. The latter results demonstrate that contrary to the findings of earlier electrophysiologic studies carried out on ventral tegmental area dopaminergic neurons, changes in the release of dopamine in projection areas occur across the sleep-wake cycle. The elevated levels of dopamine during waking and REM sleep in the medial prefrontal cortex and the nucleus accumbens could result from changes during these two states in afferent modulation at the level of cell bodies or at the level of dopaminergic terminals.

Animals↗
PubMed2004

Campylobacter fetus meningitis in a diabetic adult cured by imipenem.

Reported here is the successful management of a severe case of Campylobacter fetus subspecies fetus meningitis, complicated by septic shock, in a patient without overt immunosuppression who was cured by imipenem. Meningitis caused by C. fetus has rarely been reported in adults, and only exceptionally in non-immunocompromised patients, and septic shock has not previously been reported as a complication of such meningitis. The best antibiotic regimen for treating this condition remains to be determined. Imipenem has displayed high in vitro activity against C. fetus but has been used rarely in clinical practice. It was administered in this case with good results.

Aged↗
PubMed2004

Toward brain imaging of serotonin 5-HT1A autoreceptor internalization.

Enhancing cerebral serotonin (5-hydroxytryptamine, 5-HT) neurotransmission is a common property of antidepressant treatments and the basis for their efficacy. 5-HT1A receptors located on the cell body and dendrites of 5-HT neurons (autoreceptors) play a key role in this regard. Because they normally mediate an inhibition of neuronal firing, their desensitization is a prerequisite to the delayed enhancement of 5-HT neurotransmission upon treatment with monoamine oxidase (MAOI) inhibitors or specific serotonin reuptake inhibitors (SSRI). Using beta-sensitive microprobes in vivo, we measured a significant decrease (-30%) in binding sites for the 5-HT1A PET radioligand [18F]MPPF associated with an equivalent reduction (-34%) in the cell surface density of 5-HT1A receptor immunoreactivity (internalization), in the nucleus raphe dorsalis (autoreceptors), but not hippocampus (heteroreceptors), of rats given a single dose of the specific 5-HT1A receptor agonist, 8-OH-DPAT (0.5 mg/kg, iv). This effect was completely blocked by pretreatment with the selective 5-HT1A antagonist WAY 100635. Having ruled out that this decreased density of [18F]MPPF binding in the nucleus raphe dorsalis of 8-OH-DPAT-treated rats resulted from a local blood flow effect, we obtained autoradiographic evidence indicating that the total amount of specific binding of [18F]MPPF in tissue sections was unaffected by the 8-OH-DPAT treatment in either NRD or hippocampus. It was therefore concluded that the internalization of 5-HT1A autoreceptors accounted for the decreased binding in vivo of [18F]MPPF in the nucleus raphe dorsalis of rats treated with 8-OH-DPAT. Thus, PET imaging might provide a mean to measure 5-HT1A receptor internalization in human brain and thus assess responsiveness to antidepressant treatment.

8-Hydroxy-2-(di-n-propylamino)tetralin↗
PubMed2003

[Wakefulness and central basal nuclei: experimental observations and possible implications in Parkinson's disease].

Movement disorders in Parkinson disease, notably dampened during sleep, are associated with hyperactivity of the subthalamic nucleus (STN), whose origin is controversial. We have studied, on non-anaesthetized head-restrained rats, the STN spontaneous unit activity and the one of its principal GABAergic afferents, the globus pallidus (GP). In normal rats, STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. In contrast GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge rate whatever the vigilance state. During paradoxical sleep, both STN and GP neurons increased markedly their firing rate. When applied during W, GABA-A antagonists increased the STN firing rate but did not change the typical W random pattern. When applied during SWS, they strongly reinforced the spontaneous burst pattern into a particularly marked one with instantaneous frequencies reaching 500Hz. SWS-W transitions occurring during ongoing antagonist iontophoresis invariably disrupted this burst pattern into a random one. On 6-OHDA unilaterally treated rats, the ipsilateral STN was hyperactive whatever the vigilance state (with an abnormal burst pattern during W on some neurons), but this hyperactivity did not seem to be associated with a GP hypoactivity. These results show that STN activity is not inversely correlated with GP activity, that its discharge pattern is strongly dependent on vigilance states, that GABA receptors do not play an exclusive role in regulating its firing pattern, and question the depolarization block hypothesis during STN high frequency stimulation.

Animals↗
PubMed2002

The potential of the beta-Microprobe, an intracerebral radiosensitive probe, to monitor the [(18)F]MPPF binding in the rat dorsal raphe nucleus.

The aim of this study was to demonstrate the ability of a recently developed beta(+)-range sensitive intracerebral probe (beta-Microprobe) to measure the binding kinetics of [(18)F]MPPF, a well-documented 5-HT(1A) serotoninergic receptor ligand, in the dorsal raphe nucleus (DRN) of the anaesthetised rat. This midbrain nucleus presents a high concentration of 5-HT(1A) receptors known to be implicated in the effects of antidepressants. The difficulty confronting this study lay in the fact that the dimensions of the DRN are smaller than the detection volume of the beta-Microprobe. In the first part of the study, we studied the feasibility of this measurement from a theoretical point of view by autoradiography and a Monte Carlo simulation. We determined the optimal beta-Microprobe location close to the DRN and verified that this configuration allowed accurate determination of [(18)F]MPPF specific binding in the nucleus. In the second part of our study, we measured the in vivo time-concentration curves of [(18)F]MPPF binding in the DRN in comparison with the cerebellum. The specificity of [(18)F]MPPF binding in the DRN was confirmed by its displacement after non-labelled 5-HT(1A)antagonist injection (MPPF or WAY-100635). Moreover, we verified the feasibility of using beta-Microprobe monitoring and simultaneous validation by microdialysis to study the effect of an increase in extracellular serotonin, induced by fenfluramine injection, on [(18)F]MPPF binding in the DRN. Our theoretical simulations, confirmed by our experimental results, demonstrate the ability of this new device to monitor in vivo the binding of [(18)F]MPPF in the DRN of anaesthetised rodents.

Aminopyridines↗
PubMed2002

In vivo temporal sequence of rat striatal glutamate, aspartate and dopamine efflux during apomorphine, nomifensine, NMDA and PDC in situ administration.

In vivo microdialysis was used to investigate the interactions between dopamine (DA), glutamate (Glu) and aspartate (Asp) in anaesthetised-rat striatum. The combination of brain microdialysis and capillary electrophoresis with laser-induced fluorescence detection (CE-LIFD) allows the simultaneous monitoring of the efflux of these neurotransmitters up to every 10 s. DA and Glu reuptake inhibitors, nomifensine and L-trans-pyrrolidine-2,4-dicarboxylic acid (PDC) and, dopaminergic and glutamatergic receptor agonists, apomorphine and NMDA respectively, were administered by reverse dialysis. Reverse dialysis of 20 micro M nomifensine induced a rapid and marked increase (+3200% at 5 min) in extracellular DA, while a decrease in Glu and Asp (-11 and -25%, respectively) was observed simultaneously. Reverse dialysis of 10 micro M apomorphine led to progressive changes: -63% decrease in DA and +25% Glu increase at 36 min. Reverse dialysis of 1 mM NMDA induced a simultaneous increase in DA, Glu and Asp which peaked at +2 min (+840%, +40% and +150%, respectively). Surprisingly, a second increase in Glu was observed 5 min after the end of NMDA perfusion. Reverse dialysis of PDC (1 mM and 10 mM) induced a rapid increase in Glu and Asp levels, while DA increased with a 26-s delay. These findings indicate that, in the striatum, endogenous DA and Glu may act in opposition to regulate each other's efflux. These results have been obtained due to unique features offered by microdialysis coupled with CE-LIFD.

Animals↗
PubMed2001

Endogenous neurotensin down-regulates dopamine efflux in the nucleus accumbens as revealed by SR-142948A, a selective neurotensin receptor antagonist.

SR-142948A belongs to the second generation of potent, selective, non-peptide antagonists of neurotensin receptors. It was used to investigate the role of endogenous neurotensin in the regulation of dopamine efflux in the nucleus accumbens and striatum of anaesthetized and pargyline-treated rats. All the data were obtained using in vivo electrochemistry. Electrically evoked (20 Hz, 10 s) dopamine efflux was monitored by differential pulse amperometry, whereas variations in basal (tonic) dopamine efflux were monitored by differential normal pulse voltammetry. Like the first-generation compound SR-48692, SR-142948A did not affect the tonic and evoked dopamine efflux, but dose-dependently enhanced haloperidol (50 microg/kg, i.p.) induced facilitation of the electrically evoked dopamine release in the nucleus accumbens. In contrast to SR-48692, SR-142948A dose-dependently potentiated haloperidol (50 microg/kg, i.p.) induced increase in the basal dopamine level in the nucleus accumbens. This potentiating effect did not appear in the striatum. When dopaminergic and/or neurotensinergic transmissions were modified by a higher dose of haloperidol (0.5 mg/kg, i.p.), apomorphine, amphetamine or nomifensine, SR-142948A pre-treatment affected only the effect of apomorphine on the basal dopamine level in the nucleus accumbens. These results strengthen the hypothesis that endogenous neurotensin could exert a negative control on mesolimbic dopamine efflux.

Adamantane↗
PubMed2001

Outcomes of primary and catheter-related bacteremia. A cohort and case-control study in critically ill patients.

We studied a cohort of 2201 patients hospitalized in 15 French intensive care units (ICUs) for > or = 48 h during a 4-mo period to assess the incidence and outcomes of primary and definite catheter-related bloodstream (CRB) or secondary nosocomial bloodstream infection (NBSI). Variables associated with ICU death and duration of stay were determined by logistic regression, and attributable mortality and length of stay (LOS) from a nested matched case-control (96 pairs) study, stratified on the source of bacteremia. Bacteremia occurred in 5% (95% CI 4.1-6%) of patients with > or = 48 h ICU stay. Primary, CRB, and secondary NBSI accounted for 29%, 26%, and 45% of the 111 episodes, respectively. NBSI was associated with a markedly increased risk of death (OR = 4.6; 95% CI 2.9-7.1) and an attributable mortality of 35% (95% CI, 28%-47%). In the case-control study, the excess mortality was 20% (p = 0.03) in patients with primary bacteremia and CRB, and 55% (p < 0.001) for secondary bacteremia; in patients with CRB only, the excess mortality was 11.5%. The median excess ICU LOS in survivors of NBSI was 9.5 d, and was similar, irrespective of its source. The risk of mortality associated with primary and catheter-related bacteremia appears much lower than that of secondary bacteremia, but is sizable, and the excess LOS incurred by the various categories of bacteremia is comparable. Differentiating catheter-related bacteremia from both primary and other secondary bacteremia appears warranted in studies conducted in critically ill patients.

Bacteremia↗
PubMed2001

Microdialysis study of amino acid neurotransmitters in the spinal dorsal horn of patients undergoing microsurgical dorsal root entry zone lesioning. Technical note.

The aim of this study was to develop, for the first time in the human spinal dorsal horn (DH), an in vivo method for the study of amino acids (AAs). A microdialysis technique was used to sample AAs in the extracellular fluid of the DH apex in eight patients in whom surgery in the dorsal root entry zone (DREZ) was performed. Before making microsurgical lesions, specific concentric-type microdialysis probes were implanted over a 60-minute period in the DREZ and directed to the DH apex (10 implantations). The AA concentrations in the dialysates were determined using high-performance liquid chromatography with fluorescence detection. The concentrations of excitatory AAs (glutamate and aspartate) and inhibitory AAs (gamma-aminobutyric acid and glycine) decreased and were stabilized by 45 minutes after probe implantation, whereas the levels of nonneurotransmitter AAs (alanine and threonine) were not stabilized at 60 minutes. The ability of the probe to track the changes of extracellular AAs was demonstrated. Neither intra- nor postoperative microdialysis-related complications were observed (with a follow up of 18 months). The present study demonstrates that microdialysis can be performed safely in the human DH during DREZ lesioning. Despite technical and analytical limitations related to the intraoperative conditions, this technique offers new possibilities for clinical research on neurotransmitters involved in some relevant pathological states, especially in chronic pain and spasticity.

Adolescent↗
PubMed2000

Single-unit and polygraphic recordings associated with systemic or local pharmacology: a multi-purpose stereotaxic approach for the awake, anaesthetic-free, and head-restrained rat.

In order to avoid any artifactual pharmacological interferences with anaesthetic agents, a procedure has been developed for working on the awake, anaesthetic-free rat in a head-restrained condition. It allows, on the same animal and over several consecutive days, single-unit recordings in combination with systemic or local pharmacology (microiontophoresis or micropressure ejections), as well as monitoring vigilance states via the electroencephalogram and the electromyogram. After the cementing of a special "U"-shaped device on its skull under general anaesthesia, the animal is progressively habituated to stay daily, for several hours, under a painless corresponding stereotaxic restraint. This system can be easily adapted to different stereotaxic frames and, because of its spatial flexibility for targetting the desired rostrocaudal or lateral positions, allows access to a large number of cerebral structures. Experiments performed on Globus Pallidus, Substantia Nigra, and Locus Coeruleus neurons, combining the different possibilities of this system, are reported. They demonstrate, on the awake anaesthetic-free head-restrained rat, and under suitable ethical conditions, the feasibility of single-unit recordings of identified neurons associated with the study of their pharmacological reactivity after systemic or local drug administrations without any other drug interferences, and in physiologically relevant conditions such as the spontaneous alternance of vigilance states.

Action Potentials↗
PubMed2000

Amino acids in spinal dorsal horn of patients during surgery for neuropathic pain or spasticity.

A specific microdialysis probe combined with high performance liquid chromatography analysis was used to compare the basal levels of extracellular amino acids (AAs) in the dorsal horn (DH) between two groups of patients undergoing spinal surgery for the treatment of peripheral neuropathic pain (n = 5) or disabling spasticity (n = 5). A stabilized concentration was reached in the dialysates 45 min after probe implantation for excitatory AAs (glutamate and aspartate) and inhibitory AAs (GABA and glycine). A significant increase in the ratios aspartate/GABA and aspartate/glycine was found in the group of patients suffering from neuropathic pain. This study shows the feasibility of a microdialysis investigation in the DH of patients during a neurosurgical operation and supports in humans the hypothesis of an imbalance between excitatory AAs and inhibitory AAs within the DH in neuropathic pain states, as suggested by previous animal studies.

Amino Acids↗
PubMed2000

Comparative effects of neurotensin, neurotensin(8-13) and [D-Tyr(11)]neurotensin applied into the ventral tegmental area on extracellular dopamine in the rat prefrontal cortex and nucleus accumbens.

Ejections of 10(-5)-10(-3)M neurotensin into the ventral tegmental area increased dopamine efflux measured by electrochemical approaches in the prefrontal cortex of anaesthetized rats. In the same conditions, the effects evoked on dopamine efflux by 10(-5)M neurotensin(8-13) and [D-Tyr(11)]neurotensin were different from each other and depended on the explored area: the prefrontal cortex and the caudal and rostral nucleus accumbens. In the prefrontal cortex, neurotensin(8-13) was as potent as neurotensin, whereas [D-Tyr(11)]neurotensin was ineffective. In the caudal nucleus accumbens, when considering the initial intensity of the effect, neurotensin(8-13) and neurotensin appeared more potent than [D-Tyr(11)]neurotensin. In contrast, in the rostral nucleus accumbens, neurotensin(8-13) was less potent than [D-Tyr(11)]neurotensin and neurotensin. These results support the differential involvement of two pharmacologically distinct neurotensin receptor entities on ventral tegmental area neurons in the modulation of mesolimbic and mesocortical dopaminergic activity.

Animals↗
PubMed2000

Unrelated course of subthalamic nucleus and globus pallidus neuronal activities across vigilance states in the rat.

The pallido-subthalamic pathway powerfully controls the output of the basal ganglia circuitry and has been implicated in movement disorders observed in Parkinson's disease (PD). To investigate the normal functioning of this pathway across the sleep-wake cycle, single-unit activities of subthalamic nucleus (STN) and globus pallidus (GP) neurons were examined, together with cortical electroencephalogram and nuchal muscular activity, in non-anaesthetized head-restrained rats. STN neurons shifted from a random discharge in wakefulness (W) to a bursting pattern in slow wave sleep (SWS), without any change in their mean firing rate. This burst discharge occurred in the 1-2 Hz range, but was not correlated with cortical slow wave activity. In contrast, GP neurons, with a mean firing rate higher in W than in SWS, exhibited a relatively regular discharge whatever the state of vigilance. During paradoxical sleep, both STN and GP neurons increased markedly their mean firing rate relative to W and SWS. Our results are not in agreement with the classical 'direct/indirect' model of the basal ganglia organization, as an inverse relationship between STN and GP activities is not observed under normal physiological conditions. Actually, because the STN discharge pattern appears dependent on coincident cortical activity, this nucleus can hardly be viewed as a relay along the indirect pathway, but might rather be considered as an input stage conveying corticothalamic information to the basal ganglia.

Animals↗
PubMed1999

Evidence that the neuronal nitric oxide synthase inhibitor 7-nitroindazole inhibits monoamine oxidase in the rat: in vivo effects on extracellular striatal dopamine and 3,4-dihydroxyphenylacetic acid.

The present study investigated in vivo the kinetic of the changes in rat striatal extracellular concentrations of dopamine (DA), and its monoamine oxidase (MAO)-derived metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), following administration either of nitric oxide (NO) synthase (NOS) inhibitors 7-nitroindazole (7-NI) and Nomega-nitro-l-arginine methyl ester (L-NAME) or of the widely used MAO inhibitor pargyline. DA and DOPAC concentrations were determined every 4 min by microdialysis combined with capillary zone electrophoresis coupled with laser-induced fluorescence detection (CZE-LIFD) and by differential normal pulse voltammetry (DNPV), respectively. Administration of 7-NI, both systemic (30 mg/kg, intraperitoneally, i.p.) or intrastriatal (1 mM through the microdialysis probe), as well as administration of pargyline (75 mg/kg, i.p.), induced simultaneously in the striatum a significant increase in extracellular DA and a significant decrease in extracellular DOPAC. However, administration of L-NAME (200 mg/kg, i.p.) produced a significant increase in striatal extracellular DA without changes in extracellular DOPAC. These data suggest a possible MAO inhibitory effect of 7-NI which seems to be restricted to this NOS inhibitor. These results may be of special interest for the studies on functional role of NO in the brain, particularly in dopaminergic transmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1999

Evidence that the neuronal nitric oxide synthase inhibitor 7-nitroindazole inhibits monoamine oxidase in the rat: in vivo effects on extracellular striatal dopamine and 3,4-dihydroxyphenylacetic acid.

The present study investigated in vivo the kinetics of the changes in rat striatal extracellular concentrations of dopamine (DA), and its monoamine oxidase (MAO)-derived metabolite 3,4-dihydroxyphenylacetic acid (DOPAC), following administration either of nitric oxide (NO) synthase inhibitors 7-nitroindazole (7-NI) and N(omega)-nitro-L-arginine methyl ester (L-NAME) or of the widely used MAO inhibitor pargyline. DA and DOPAC concentrations were determined every 4 min by microdialysis combined with capillary zone electrophoresis coupled with laser-induced fluorescence detection (CZE-LIFD) and by differential normal pulse voltammetry (DNPV), respectively. Administration of 7-NI, both systemic (30 mg/kg, i.p.) or intrastriatal (1 mM through the microdialysis probe), as well as administration of pargyline (75 mg/kg, i.p.), induced simultaneously in the striatum a significant increase in extracellular DA and a significant decrease in extracellular DOPAC. On the other hand, administration of L-NAME (200 mg/kg, i.p.) produced a significant increase in striatal extracellular DA without changes in extracellular DOPAC. These data suggest a possible MAO inhibitory effect of 7-NI which seems to be restricted to this NOS inhibitor. These results may be of special interest for the studies on the functional role of NO in the brain, particularly in dopaminergic transmission.

3,4-Dihydroxyphenylacetic Acid↗
PubMed1998

Coupling on-line brain microdialysis, precolumn derivatization and capillary electrophoresis for routine minute sampling of O-phosphoethanolamine and excitatory amino acids.

In previous papers, we described the analysis of excitatory amino acids (EAAs) and catecholamines in microdialysis samples using capillary electrophoresis with laser-induced fluorescence detection (CE-LIFD). In the present paper, we report that an automated analysis of such samples can be easily achieved by on-line coupling of the microdialysis probe with a continuous flow derivatization system and a commercially available CE-LIFD apparatus. Because of the short analysis time (less than 2 min) and high separation efficiency (100-200,000 theoretical plates), high temporal resolution of microdialysis (minute range) is preserved as compared to off-line systems, while both EAAs and O-phosphoethanolamine (PEA) can be simultaneously detected. This new method has been applied to the measurement of these compounds in microdialysis samples from hippocampal slice cultures and striatum of anesthetized rats. Extracellular concentrations of EAAs, but not PEA, increased during perfusion of a solution containing high K+ or a glutamate uptake inhibitor. However, after in vitro ischemia on hippocampal slices, both EAAs and PEA concentrations increased, but with different temporal patterns.

Animals↗
PubMed1998

Biological parameters in major depression: effects of paroxetine, viloxazine, moclobemide, and electroconvulsive therapy. Relation to early clinical outcome.

BACKGROUND: Clinical and pharmacologic studies report a relative or absolute serotonergic deficiency in major depression; however, the variability of clinical characteristics of illness has led to controversial results. In the present work, we looked for a possible relationship between i) biochemical values that indirectly reflect aminergic neurons activity and clinical characteristics and ii) their evolution and the early clinical outcome under antidepressive therapies (ATs). METHODS: Platelet serotonin content, platelet monoamine oxydase activity, and urinary biopterins were measured in 27 depressed patients before and during four different ATs (paroxetine, viloxazine, moclobemide, or electroconvulsive therapy). Depressive symptomatology and its evolution under ATs were quantified using three clinical rating scales. RESULTS: A severe symptomatology, high serotonin (5-HT) platelet content, and high or low urinary B could represent risk factors leading to a smaller or delayed response to an AT. Furthermore, the early improvement under ATs was negatively correlated to pretreatment 5-HT platelet content. CONCLUSIONS: Determination of 5-HT level could be useful in the choice of an AT.

Adrenergic Uptake Inhibitors↗