Biomedical subjects

M Lerner-Natoli

Publications and source records attributed to M Lerner-Natoli.

34 records · Page 2Linked to original sources

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↗

PubMed1990

Catecholaminergic systems and amygdala kindling development. Effects of bilateral lesions of substantia nigra dopaminergic or locus coeruleus noradrenergic neurones.

The effects of the bilateral and selective destruction of substantia nigra (SN) dopaminergic or locus coeruleus (LC) noradrenergic neurones, consecutive to a local injection of 6-hydroxydopamine, were studied on the development of amygdala kindling. Immunohistochemical controls of lesions were performed using selective dopamine (DA) or norepinephrine (NE) antibodies. The results demonstrated that a massive destruction of SN pars compacta neurones did not modify the rate of kindling development. Conversely, the lesions of LC neurones (sparing lateral tegmental nuclei) markedly facilitated the development of amygdala kindling. This effect was related to the extent of NE denervation. Together, these results suggest that DA is not strongly involved in the development of kindling, and that the nigrostriatal output does not play a major role in the generalization of kindled seizures. In contrast, they confirm an inhibitory influence exerted by LC noradrenergic ascending pathways on the development of kindling.

Amygdala↗

PubMed1990

["Wet dog shakes" during olfactory bulb kindling].

Kindling phenomenon provides an experimental model of limbic secondarily generalized epilepsy. It can be easily obtained by stimulation of the olfactory bulb (OB) which is strongly connected to limbic structures. The after-discharge induced by subconvulsant electrical stimulations, is followed by a behavioral phenomenon, named Wet Dog Shakes (WDS). In the course of the Rat OB kindling, the development of WDS is biphasic: 1) an ascendant phase during the first three stages, and 2) a descendant phase in the stages 4 and 5, that may give evidence of the installation and the intensification of the kindling process. The significance of this behavior in seizure generalization is discussed.

Animals↗

PubMed1989

[Excitotoxic damage of the hippocampus in the rat: involvement of N-methyl-D-aspartate receptors].

The intrahippocampal injection of two agonists of excitatory aminoacid (EAA) receptors elicited neuronal damages localized in CA1 and dentate gyrus for N-methyl-D-aspartate (NMDA) (20 nmol) and extended to the various hippocampal areas, except dentate gyrus for kainic acid (KA) (2.5 nmol). The pretreatment of the animals with N-[1-(2-thienyl)cyclohexyl]piperidine (TCP) (20 mg/kg), a noncompetitive NMDA-receptor antagonist, prevented the neuronal injury induced by NMDA and KA in CA1. The distribution of neuronal damages and of TCP-protected areas closely correlated to that of EEA-receptors and of TCP binding sites in the hippocampus.

Animals↗

PubMed1987

Wet dog shakes in limbic versus generalized seizures.

Wet dog shake behavior was studied in different models of epilepsy in the rat. Numerous wet dog shakes were associated with limbic seizures in the course of focal epilepsy induced by kindling stimulations or local injections of kainic or quisqualic acid and progressively disappeared during generalization. On the contrary, they were never observed in models of generalized epilepsy. This study suggests that the number of wet dog shakes may be an index of the progression of limbic seizures toward generalization.

Amygdala↗

PubMed1987

Serotonin and kindling development.

The inhibitory effect of serotonin on the kindling model of epilepsy was investigated in the adult rat. Specific neurotoxins such as 5-6 or 5-7 dihydroxytryptamine were used to destroy serotoninergic neurons before kindling sessions, and an immunocytochemical control revealed, at the end of the experiments, the location and the extent of the lesions. The destruction of serotoninergic terminals in the epileptic focus (olfactory bulb or amygdala) facilitated the initial development of kindling obtained by stimulations of these structures. Lesions of pontis, centralis and dorsalis nuclei of the raphe enhanced the rate of olfactory bulb kindling. Finally, we transplanted foetal raphe cells into the olfactory bulb of adult rats before olfactory bulb kindling. The presence of viable grafts, controlled by immunocytochemistry, was associated with an increase of afterdischarge threshold in the olfactory bulb. All these results confirm the inhibitory function of serotonin on kindling development and demonstrate that serotoninergic neurons exert an important control both on local excitability and on the progressive establishment of kindling phenomena.

5,6-Dihydroxytryptamine↗

PubMed1986

Facilitation of olfactory bulb kindling after specific destruction of serotoninergic terminals in the olfactory bulb of the rat.

The role of serotonin (5-HT) in the kindling model of epilepsy was investigated by performing specific lesions of the 5-HT innervation at the level of the primary epileptogenic focus. We injected bilaterally 5,6-dihydroxytryptamine in the olfactory bulb (OB) of adult rats which were submitted to electrical stimulations of the OB until the occurrence of stage-5 seizures. Immunohistochemical controls of lesions were realized with a specific anti-5-HT antibody. Results revealed that the lesions facilitated the initial development of kindling (increase of afterdischarge duration and of kindling rate), suggesting that 5-HT terminals exert a modulatory effect on the propagation of the epileptic activity.

Animals↗

PubMed1986

[Specific lesions of serotoninergic cells in the raphe. Effect on kindling of the olfactory bulb in rats].

Limbic kindling obtained by electrical stimulation of the olfactory bulb in the rat has been studied after specific lesion of serotonergic cells in mesencephalic and pontic raphe nuclei with local microinjection of 5,7-dihydroxytryptamine. The extent of the raphe lesions was verified by immunocytochemical technics with antiserotonin antibody. Lesioned rats showed an increase of kindling rate, which confirms the inhibitory function of serotonin in the development of this phenomenon.

5,7-Dihydroxytryptamine↗

PubMed1986

[Transplantation of serotonin neurons in the olfactory bulb of the adult rat].

Serotonergic neurons have their perikaraya concentrated in the raphe nuclei. In the present experiment, pieces of raphe nuclei containing serotonergic neuroblasts were dissected from 14 days rat embryos, mechanically dissociated, and 1 microliter of a cell suspension containing 30,000 cells was injected slowly under stereotaxic control in the olfactory bulb of adult rats. Three weeks after transplantation, the brain of the rats were processed for immunocytochemical detection of 5-HT. In all of the grafted animals, 5-HT neurons were found in the olfactory bulb. They exhibited the morphology of adult neurons, with well developed axon and dendrites, extending far from the injection site. Ultrastructural immunocytochemistry disclosed afferent and efferent synapses to the grafted neurons. Three preliminary results indicates that the transplanted neurons have been integrated in the host's neuronal circuitry. Ongoing electrophysiological studies are now directed at investigating the functional status of these grafted neurons.

Animals↗

PubMed1985

Absence of modifications in gamma-aminobutyric acid metabolism after repeated generalized seizures in amygdala-kindled rats.

Alterations in gamma-aminobutyric acid (GABA) metabolism have been investigated in the kindling model of epilepsy. Numerous generalized seizures were induced by amygdala-kindling stimulations in rats. One week after the last stimulation, there were no changes in GABA levels nor in the activity of enzymes responsible for the synthesis (glutamic acid decarboxylase) and catabolism (GABA transaminase and succinyl semialdehyde dehydrogenase). These results do not exclude other changes in GABA function as modifications of transport or receptors.

4-Aminobutyrate Transaminase↗

PubMed1984

Hippocampal kindling in the rat: intrastructural differences.

Kindling patterns were compared in different regions of the hippocampus of the rat. The duration, morphology, and frequency of the electrical responses were different after stimulation of the dorsal and the ventral hippocampus, but these parameters showed the same evolution as kindling progressed. Comparison of the threshold intensity and of the kindling rate revealed some differences not only between dorsal and ventral hippocampus, but also within the dorsal hippocampus: The central layers had higher thresholds and longer kindling periods than the outer layers and the fimbria hippocampi. We suggest that stimulation of hippocampal efferents is responsible for the greater ease of kindling in the outer layers than in the central regions of this structure. The degree of connection of the different parts of the hippocampus with the amygdala and the influence of the intrinsic inhibitory GABAergic circuitry are discussed.

Action Potentials↗

PubMed1984

Evolution of wet dog shakes during kindling in rats: comparison between hippocampal and amygdala kindling.

The occurrence of wet dog shakes (WDS) was studied during hippocampal kindling and amygdala kindling. Many WDS were observed after the first stimulation of the dorsal and ventral hippocampus. Their number rapidly increased to a maximal value (after five to six stimulations) and then progressively decreased during the development of hippocampal kindling. Their distribution during the afterdischarge (AD) was impaired by kindling. During amygdala kindling, WDS were observed only when the ADs attained a total duration of at least 50 s. In this case too, the repetition of stimulations was concomitant with a progressive decrease in the number of WDS. We suggest that the regression of the number of WDS may be considered as an additional criterion of the fully kindled state.

Amygdala↗

PubMed1984

[Changes in benzodiazepine receptors in the limbic system following kindling of the olfactory bulb in rats].

Repeated electrical stimulations of the olfactory bulb led to the progressive development of a generalized epilepsy (kindling effect). One week after the last stimulation eliciting a stage 5 seizure, diazepam-(3H) binding was studied in olfactory bulb-kindled rats. Numbers of benzodiazepine receptors were increased in kindled olfactory bulb and amygdala. No significant change was observed in hippocampus. This modification could be considered as a response of the inhibitory mechanisms to repeated seizures which is insufficient to counteract the installation of the kindling effect.

Animals↗

PubMed1983

[Wet-dog shaking behavior in rats in hippocampal kindling].

The kindling phenomenon, induced by repetitive electrical stimulation of the hippocampus of the rat is associated with the production of a particular behavior: the Wet Dog Shakes (WDS). The evolution of WDS is strongly and negatively correlated with the intensification of motor seizures. Some differences can be seen in the occurrence of WDS according to whether the stimulation is applied in dorsal or in ventral hippocampus. Although the anatomical substrate responsible for this behavior is not clearly defined, the relationship between WDS and kindling let us consider it as an index of the generalization of the epilepsy.

Animals↗

PubMedDate not supplied

[The role of nitric oxide and superoxides in the neurotoxicity of glutamate].

Glutamate is the major neurotransmitter of the mammalian brain. Stimulation of glutamate receptors, especially the subgroup of NMDA receptors, induces nitric oxide and arachidonic acid synthesis in neurons. These agents freely diffuse across membranes and thus can play roles of messengers in particular brain functions. The aim of our study was to identify these roles in in vitro and in vivo models from mouse and rat. Exaggerated stimulation of NMDA receptors leads to neurological disorders such as some types of epilepsy and neurodegenerative diseases. We show that superoxide ions, which probably result from metabolic degradation of arachidonic acid, would be responsible of the neurotoxic action of NMDA. On the other hand, we observed that nitric oxide inhibits NMDA receptors. This effect would protect animals against epileptic and neurodegenerative diseases mediated by over-stimulation of these receptors. This endogenous regulation may play important roles in the functioning of glutamatergic neurotransmission.

Animals↗