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Biomedical subjects

G Rondouin

Publications and source records attributed to G Rondouin.

At least 37 records · Page 2Linked to original sources
PubMed1995

Removal of adrenal steroids from the medium reverses the stimulating effect of catecholamines on corticotropin-releasing hormone neurons in organotypic cultures.

An organotypic culture system of anterior hypothalamic slices was developed for studying the secretory responses of corticotropin-releasing hormone (CRH) neurons to corticosteroid-catecholamine interactions. The standard culture medium included 5% horse serum containing 50 micrograms/l cortisol. In 1- to 3-day cultures, the tissue viability was demonstrated by the presence of arginine vasopressin immunolabeled perikarya and axons in the paraventricular nucleus and by sustained tissue concentrations of CRH (around 50 pg/mg protein). However, immunoreactive CRH neurons were not detectable in cultures in the standard medium. Exposure of cultures to high K+ (56 mM) in the medium induced a ten-fold increase in basal CRH release which was completely abolished in a Ca(2+)-free medium containing 2 mM EGTA. Noradrenaline (NA) triggered CRH release in a dose-dependent (1-20 microM) and time-dependent (0.5-6 h) manner. Removal of corticosteroids from the media by charcoal treatment led to (1) the visualization of immunolabelled CRH perikarya and fibers and a 55% rise in CRH content of the paraventricular nucleus tissue and (2) to a five-fold increase in CRH release. Both effects were reversed by supplementation of the culture medium with corticosterone (50 micrograms/l). Under steroid-free conditions, NA (1-10 microM) not only failed to induce CRH release, but strongly inhibited the consistent baseline in CRH release. This was reminiscent of a similar corticosteroid-dependent inversion of the NA effect on the hypothalamic-pituitary-adrenal axis described in vivo. Overall, these results are direct evidence of complex corticosteroid-catecholamine interrelationships as major regulatory factors of the hypothalamic-pituitary-adrenal axis.

Adrenal Cortex Hormones↗
PubMed1994

NADPH diaphorase-positive cells in the brain after status epilepticus.

Using NADPH-diaphorase (NADPH-d) histochemistry, the expression of nitric oxide synthase (NOS) was studied in the rat brain 1 week after kainate-induced status epilepticus. Major changes were observed in the hippocampi of epileptic animals, especially a loss of NADPH-d positive fibres in the periphery of degenerative pyramidal cells, the survival of NOS-containing interneurones in the dentate hilus, a different pattern of NADPH-d staining in lesioned areas, probably corresponding to the expression of inducible NOS by glial cells and an increased staining of the vasculature. These different sources of NO may exert different functions in the epileptic focus.

Animals↗
PubMed1994

Kainate-induced status epilepticus leads to a delayed increase in various specific glutamate metabotropic receptor responses in the hippocampus.

Neuronal loss and gliosis were detected in the rat hippocampus soon after unilateral intra-amygdala injection of kainate (KA) (2.5 nmol) while solid mossy fiber sprouting could be seen only fourteen days after this injection. Using this experimental model, we examined the metabotropic glutamate receptor (mGluR)-induced inositol phosphate (IP) formation in hippocampal synaptoneurosomes and slices. In synaptoneurosomes prepared from ipsilateral hippocampi fourteen days following injection, there were no significant changes in mGluR- and carbachol(CARB)-stimulated IPs syntheses when sham-operated and KA-injected animals were compared. In the corresponding hippocampal slices, significant increases of the mGluR responses mediated by ibotenate (IBO) and aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD) were noted after KA application. The net stimulation values respectively expressed in a pair-wise fashion for buffer-injected control and KA-treated animals were IBO: 1,947 +/- 457 and 10,553 +/- 1,242; t-ACPD: 1,557 +/- 662 and 9,449 +/- 2,251 dpm/mg protein respectively. Significantly augmented mGluR responses in hippocampal slices were also measured at 7, 42 and 92 days after KA injection. There were, however, no significant increases in CARB-stimulated phosphoinositide hydrolysis in the hippocampal slices at all time-intervals after KA administration. These findings show that there are differences between the mGluR responses in hippocampal synaptoneurosome and slice preparations, suggesting the presence of two distinct populations of mGluR in each of these two models. The large specific increases in certain mGluR activities after KA-induced status epilepticus in hippocampal slices could represent one of the molecular mechanisms which underlie the profound morphological changes, in particular gliosis or mossy fiber sprouting, which follow the KA-induced status epilepticus.

Animals↗
PubMed1994

On time delay estimation of epileptic EEG.

The present study deals with comparative evaluation of various methods for time delay estimations applied to multichannel seizure EEG. The different methods included block algorithms, both in time and frequency domains (such as General Crosscorrelation, FFT, AR), and a new method for time delay estimation based on adaptive least-squares filtering. The various time delay estimators were tested on simulated signals and on real multichannel EEG recorded from rats having generalized seizures with focal onset. The adaptive least-squares filtering (the lattice-ladder type) has been found as the most efficient for time delay estimation.

Algorithms↗
PubMed1994

Anticonvulsant and antilethal effects of the phencyclidine derivative TCP in soman poisoning.

The protection afforded by TCP (thienylcylohexylpiperidine), a non-competitive blocker of N-methyl-D-aspartate (NMDA) receptors, against the seizures and lethality produced by 2 x LD50 of soman (62 micrograms/kg, sc), an irreversible inhibitor of cholinesterase, was studied in guinea-pigs. In the presence of additional anticholinergic medication (pyridostigmine: 0.2 mg/kg, sc, 30min prior to soman; atropine sulphate: 5mg/kg, im, 1 min post-soman), TCP pretreatment (2.5mg/kg, im, 30 or 15 min prior to soman) did not generally prevent the appearance of soman-induced status epilepticus but did arrest it after 30-40 min in 80% (TCP-30min) or 100% (TCP-15min) of the convulsing subjects. Moreover, in all subjects treated curatively, TCP was able to interrupt ongoing status epilepticus in approximately 20, 10 or 8 min when it was administered 5, 30 or 60min respectively after the onset of epileptiform tracings on EEG. All of these curatively administered animals survived and recovered remarkably well. On every criteria examined (latency-to-seizure arrest, 24hr-survival rate, clinical recovery), injection of 2.5mg/kg TCP after 90min of seizures appeared slightly less efficient compared to earlier curative administration. Therefore, our study (a) establishes that the previously reported capacity of MK-801 (dibenzocyclohepneimine) to counteract soman toxicity is not unique and could be extended to other non-competitive inhibitors of NMDA receptors; (b) shows that TCP could easily prevent and, above all, interrupt soman-induced seizures; furthermore, TCP appears the first compound ever tested on soman poisoning that still displays satisfactory anticonvulsant activity after such a long duration of initial status epilepticus (90min); therefore, TCP might be of special value for the delayed therapy for soman poisoning; (c) confirms that NMDA receptors are involved in the maintenance of seizures and play an important role in other processes implicated in the overall toxicity (including the lethal respiratory effects) of soman poisoning.

Animals↗
PubMed1993

L-nitroarginine, an inhibitor of NO synthase, dramatically worsens limbic epilepsy in rats.

During status epilepticus provoked by an intra-amygdala injection of kainic acid, the severity of seizures and of consequent neuronal damage was considerably increased in rats treated with L-NOARG, at a dose which completely inhibited NO synthesis. We propose that the effects of L-NOARG could be related to the loss of a retrograde inhibition exerted by NO on NMDA receptors. The complete suppression of NO formation in the brain finally facilitated the development and the generalization of seizures and their neurotoxic consequences.

Amino Acid Oxidoreductases↗
PubMed1992

Kindling and electrode effects on the benzodiazepine receptors density of olfactory bulb and hippocampus after olfactory bulb kindling.

The olfactory bulb (OB) kindling is a model of limbic secondary generalized epilepsy. Ten days after the completion of OB kindling, we have studied the long term effects of both electrode insertion and kindling on the binding of [3H]diazepam to crude mitochondrial fractions. On the one hand, we have shown that electrode implantation in sham-operated controls induced an obvious increase in benzodiazepine (BZD) receptor density (Bmax) only at the site of the electrode in comparison to sham-unoperated rats. These results might indicate an additional mechanism extending earlier observations reported by others, who have shown that prolonged electrode implantation induced changes in sham-operated and kindled rats. On the other hand, the long lasting effect of OB kindling on the binding parameters of [3H]diazepam was examined in the focus and in the hippocampus. The results indicate a bilateral increase of BZD receptors in the OB and an ipsilateral increase in the hippocampus. These changes might be a regulation phenomenon in response to a hyperexcitability state and to focal stimulations.

Animals↗
PubMed1992

Sleep deprivation in narcoleptic subjects: effect on sleep stages and EEG power density.

Sleep of 8 narcoleptic and 8 control subjects was recorded under baseline (i.e., prior wakefulness 16 h) and after 24 h without sleep. During both baseline and recovery total sleep time and stage 2 non-REM sleep were significantly decreased in narcoleptic subjects. Slow wave activity (i.e., EEG power density in the range of 0.75-4.5 Hz) decayed exponentially during baseline and after sleep deprivation in both narcoleptic and control subjects. During both baseline and recovery EEG power density in delta and sigma frequencies in non-REM sleep was enhanced in narcoleptic subjects relative to controls. In REM sleep differences in the same direction were present in delta and beta frequencies. After sleep deprivation EEG power density in non-REM sleep was elevated in delta and some higher frequencies in both patients and controls, but the response to sleep deprivation was stronger in narcoleptic subjects. These data show that in narcoleptic subjects regulatory processes underlying non-REM sleep homeostasis are operative and indicate that the response to sleep deprivation is stronger than in control subjects.

Adolescent↗
PubMed1992

A nitric oxide (NO) synthase inhibitor accelerates amygdala kindling.

In response to NMDA receptor activation, hippocampal, striatal and cerebellar neurons synthesize nitric oxide (NO), which in turn elevates cGMP levels via guanylate cyclase. NO is increasingly being considered as a transsynaptic retrograde messenger, involved in neuronal plasticity. The effect of an inhibitor of NO synthase, L-NG-nitroarginine (NOArg), was studied on amygdala kindling and on kindled seizures in rats. NOArg increased kindling rate, particularly in its initial period, but did not modify seizure severity in previously kindled rats, although we have no definitive explanation for this effect. However, an enhanced post-synaptic excitability could be attributed to the blockade of the negative feed-back exerted by NO on the NMDA receptor.

Amino Acid Oxidoreductases↗
PubMed1992

Chronic NO synthase inhibition fails to protect hippocampal neurones against NMDA toxicity.

Since nitric oxide (NO) is supposed to mediate excitotoxicity in various brain structures, the effects of two NO synthase inhibitors were studied on rat hippocampal lesions induced by the focal injection of N-methyl-D-aspartate (NMDA). Although both drugs (NG-nitro-L-arginine methyl ester: L-NAME and L-NG-nitroarginine: L-NOARG) were given twice daily for 4 days before NMDA injection, at doses which are known to profoundly inhibit NO synthase activity, no significant decrease of NMDA-induced damage could be observed. These results do not confirm the current hypothesis of a NO involvement in NMDA toxicity at least on hippocampal neurons, in vivo.

Amino Acid Oxidoreductases↗
PubMed1992

On the tracking of rapid dynamic changes in seizure EEG.

Estimation of autospectra and coherence and phase spectra of seizure EEG, using the FFT technique, will cause "smearing" of the rapid dynamic changes which occur during the seizure. This is inherent to FFT spectral estimation, due to the averaging process which is necessary in order to get consistent spectral estimates. A different approach suggested in the present study is to carry out multivariate autoregressive modeling of the multichannel seizure EEG, combined with adaptive segmentation. In order to obtain good estimates in cases of short record length, the vectorial AR modeling was based on residual energy ratios. The method has been tested on multichannel seizure EEG recordings from rats with focal epilepsy, caused by intracerebral administration of Kainic acid, and in depth EEG recordings in patients with temporal lobe epilepsy.

Animals↗
PubMed1991

Effect of amygdaloid kindling on the high- and low-affinity [3H]TCP binding sites of the rat CNS.

The regulation of the binding sites of [3H]TCP, a non-competitive ligand of the N-methyl-D-aspartate (NMDA) receptor, was studied on membranes prepared from different CNS regions of amygdaloid-kindled rats. The high-affinity binding sites (KdH = 4.2-7.4 nM), identified as the NMDA-gated ion channels, were not affected by kindling or by a daily injection of TCP (5 mg/kg before each electrical stimulation) which prevented kindling. These results suggest that the NMDA receptors participate to the establishment and not to the permanence of kindling. Kindling increases the number of low affinity [3H]TCP binding sites in the hippocampus (+21%, P less than 0.01) without change of the affinity (KdL = 340 nM). In the striatum both KdL and BmaxL were increased (3.3-4.4 fold, P less than 0.001) in animals pretreated with TCP before each electrical stimulation for 20 days. These last results argue in favour of a function of the low-affinity [3H]TCP binding sites, the nature of which remains to be determined.

Amygdala↗
PubMed1991

N-[1-(2-thienyl)cyclohexyl]-piperidine (TCP) does not block kainic acid-induced status epilepticus but reduces secondary hippocampal damage.

Distant damage, localized in the CA3 and CA1 areas, was observed in the hippocampus of rats as a consequence of status epilepticus (SE) induced by the injection of 2.5 nmol of kainic acid (KA) into the amygdala. In animals pretreated with an intraperitoneal injection of the non-competitive antagonist of the N-methyl-D-aspartate receptor, N-[1-(2-thienyl)cyclohexyl]-piperidine (TCP) (20 mg/kg), distant neuronal damage was reduced (CA1 neurons were always spared) whereas the rats still developed SE with an earlier onset. These results demonstrate the protective effect of TCP and confirm that epileptic activity and brain damage may be dissociated by NMDA receptor antagonists.

Animals↗
PubMed1990

Evidence that superior colliculi are involved in the control of amygdala-kindled seizures.

The effects of bilateral high radiofrequency lesions of superior colliculus (SC) were studied on amygdala kindling. The results demonstrate that a selective destruction of the SC only slightly facilitated the development of kindling. However, the most remarkable effect was the increase of afterdischarge and motor seizure duration observed when SC-lesioned animals reached the generalized seizures. These data confirm that the superior colliculi participate in controlling the generalization of kindled seizures.

Amygdala↗
PubMed1990

TCP shortens the latency of onset of isoelectricity in hypoglycaemia and fails to protect striatal neurones and dentate gyrus granule cells from hypoglycaemic injury in rats.

Competitive N-methyl-D-aspartate (NMDA) receptor antagonists are known to protect neurones against hypoglycaemic damage. We tested N-[1-(2-thienyl)cyclohexyl]piperidine (TCP), a non-competitive NMDA antagonist, in a recovery model of hypoglycaemic coma in the rat. Administered concomitantly with insulin, TCP shortened the latency of onset of electrocerebral silence, and failed to prevent striatal and dentate gyrus hypoglycaemia-induced injury. This effect is probably related to an increase in glucose consumption of neurones: TCP enhances energy metabolism in several brain structures, which could facilitate, at low blood glucose levels, the onset of isoelectricity, and hamper a putative neuro-protective effect of the drug.

Animals↗
PubMed1990

Anticonvulsive properties of F1933 (dulozafone) on kindled seizures in the rat.

The anticonvulsive properties of a new compound: F1933 (Dulozafone) were investigated in the amygdala kindling model and compared with those of diazepam. Both drugs protected fully kindled rats against generalized seizures but failed to suppress partial ictal events (amygdala afterdischarges and limbic seizures). The anticonvulsive action of F1933, administered at the ED100, was nearly reversed by the specific antagonist of benzodiazepines receptors; R015-1788 (Flumazenil), suggesting that the effect of F1933 is mediated by this receptor. These results also emphasize the usefulness of kindling to test antiepileptic drugs and to confirm their supposed profile of action.

Acetanilides↗
PubMed1990

Transplantation of serotonergic neurons into the 5,7-DHT-lesioned rat olfactory bulb restores the parameters of kindling.

In order to restore a normal pattern of kindling, kindled rats, previously lesioned in the olfactory nuclei with 5,7-dihydroxytryptamine, were grafted with serotonin (5-HT) neurons in the right olfactory bulb and then implanted for kindling procedure. It was observed that complete 5-HT lesions accelerated the kindling profile, and that the transplants containing 5-HT neurons restored, in lesioned rats, quite normal parameters.

5,7-Dihydroxytryptamine↗