PubMed HealthSearch

Biomedical subjects

C Menini

Publications and source records attributed to C Menini.

At least 37 records · Page 2Linked to original sources

Anticonvulsant effects of localized chronic infusions of GABA in cortical and reticular structures of baboons.

We studied the effects of chronic (7 day) infusions of GABA (100 and 20 micrograms/microliter, 10 microliter/h) applied in different cerebral structures of baboons made photosensitive by a subconvulsant dose of allylglycine. The GABA infusion has partial anticonvulsant effects when applied to the motor cortex, reticular magnocellular nucleus (RMC), or substantia nigra (SN), but when directed to the prefrontal cortex (area 8) it has no effect. These anticonvulsant effects of GABA infusion are more important when GABA is infused into the motor cortex, where paroxysmal discharges (PDs) originate, than when it is infused into the RMC. In contrast, the anticonvulsant effects on light-induced generalized seizures are more pronounced when GABA is infused into the RMC than when it is infused into the motor cortex. GABA infusion into the SN has no effect on PDs and myoclonia and blocks seizures less effectively than the RMC infusion. These results are in accordance with the role of the motor cortex as a generator of PDs and of RMC in the generalization of seizures. Focal paroxysmal EEG and clinical activities, previously reported to appear at the end of the motor cortex GABA infusion, were not observed after RMC or SN infusions. However, behavioral hyperactivity occurring at the end of subcortical GABA infusions was observed. These behavioral signs could correspond to the clinical expression of a GABA withdrawal syndrome.

Animals

Epileptogenic gamma-aminobutyric acid-withdrawal syndrome after chronic, intracortical infusion in baboons.

We studied the effects of chronic (7 days) infusion of GABA (100 micrograms/microliter) applied intracortically into the fronto-rolandic (FR) area of baboons, via osmotic minipumps. In photosensitive animals, bilateral GABA application produced a complete blockade of the paroxysmal discharges and associated clinical signs induced by intermittent light stimulation. Unilateral administration had similar effects, although these developed more gradually. At the end of the infusion period, both photosensitive and non-photosensitive animals showed a transitory state (3-4 days) of cortical hyperexcitability (spontaneous epileptogenic activity) localized to the infused area. The data indicate a role of GABA both in the natural photosensitivity of the epileptic baboon and in the withdrawal syndrome consecutive to the sudden interruption of chronically enhanced GABA levels in the FR territories of this monkey.

Animals

Photic epilepsy problems raised in man and animals.

The data gathered in 30 years' study in man and in several animal species, but especially in the Papio papio baboon, tend to show that the cortex plays a decisive part in the seizure and interval discharges induced by intermittent light stimulation in photic epilepsy. Two regions of the cortex predominate: the frontorolandic and occipital regions. The cortical cortex can, indeed, transmit or control the visual input to the frontorolandic region and can cause intermittent discharges in certain specific conditions in baboons and in certain human patients. The corticocortical pathway conveys the visual impulses to the frontorolandic cortex and is certainly modulated by deep structures like the reticular systems and the thalamus. At present no more can be said since further research is needed.

Animals

Stimulus-sensitive myoclonus of the baboon Papio papio: pharmacological studies reveal interactions between benzodiazepines and the central cholinergic system.

The baboon Papio papio develops a nonepileptic myoclonus 20 to 30 min after i.m. benzodiazepine injection. It is characterized by bilateral jerks involving mainly the neck and the trunk, by the absence of any correlative EEG paroxysmal discharge, and by its facilitation during movement or agitation. This myoclonus resembles the intention myoclonus of human patients as seen, for example, after anoxia. We found in experiments on 10 adolescent baboons that atropine alone induced the myoclonus for several hours, that physostigmine completely antagonized the benzodiazepine-induced as well as the atropine-induced myoclonus, and that the peripherally acting cholinergic antagonist, methyl-QNB, and agonist prostigmine had no action on the myoclonus, suggesting that the benzodiazepine-induced myoclonus in this species depends on a strong depression of the central cholinergic system by benzodiazepine. The benzodiazepine-induced myoclonus was mediated by benzodiazepine receptors as it was blocked by the specific benzodiazepine receptor antagonist, Ro 15-1788, which did not block atropine-induced myoclonus; latency to myoclonus after benzodiazepine was longer than after atropine. These facts suggest that benzodiazepines, by an as yet unknown mechanism, induce a depression of the cholinergic system which in turn leads to the development of myoclonus. Finally, the benzodiazepine-induced myoclonus of the baboon can be considered as a good model for testing drugs that act on the muscarinic cholinergic system and also for testing benzodiazepine-acetylcholine interactions.

Animals

[Analysis of the multi-unit activity of the cortex and subcortical structures during paroxysmal discharges and grand mal seizures in the photosensitive baboon].

Cortical and subcortical multiunitary activities (MUA) and EEG were simultaneously recorded in baboons rendered photosensitive by a subconvulsant dose of DL-allylglycine. Intermittent light stimulation (ILS) trains induce in those animals fronto-rolandic (FR) paroxysmal discharges (PDs, constituted as spikes and waves) and grand mal seizures. During the induction of FR PDs by ILS trains, the visual structures (occipital cortex, colliculi superioris, pulvinar) show a significant MUA increase which is not related to the PD spike or wave but is correlated to the flashes. The first structure showing bursts of MUA that frequently precede the PD appearance is the FR cortex. When PDs appear, the bursts are related to the spikes of PDs and are followed by an inhibition during the slow wave. The pontine and mesencephalic reticular formations and the facial nuclei are activated in bursts after the FR PDs have reached a certain amplitude. The thalamic nuclei ventralis lateralis, centrum medianum and lateralis posterior are activated only later, when the FR PDs have reached an even greater amplitude. It is suggested that the activation of visual structures is necessary for FR PD appearance. The secondary pontine and mesencephalic activation could reinforce that of the FR cortex and then the thalamus, and could determine the myoclonus observed in unparalyzed animals.

Allylglycine

[Myoclonia. From the myoclonia of Papio papio to various human myoclonias].

The baboon Papio papio is naturally predisposed to present several types of myoclonus, the study of which can help in understanding the various human myoclonic symptomatologies. The three types of myoclonus which are studied have been called A, B and C. Myoclonus A, which is induced by intermittent photic stimulation in photosensitive animals, is of epileptic nature: It is always preceded by spikes-waves predominating in the fronto-rolandic cortex (areas 4 and 6) and can be followed by secondarily generalized tonic-clonic seizures. Myoclonus B, which occurs when the animal is agitated, is facilitated by somatic stimulations. Since it is never preceded or accompanied by spikes-waves and since it is never associated with epileptic seizures, myoclonus B is considered as non-epileptic. Myoclonus C occurs during wave-sleep. They are associated with spikes-waves during the slow but not during paradoxical sleep. Myoclonus A, B and C can co-exist in the same animal when it is photosensitive. Myoclonus B and C can co-exist in the same animal when it is non-photosensitive. Clinically, the three types of myoclonus have different symptomatologies. Myoclonus A is bilateral and synchronous. It always involves initially the eyelids and face. It can secondarily become generalized to the whole body. Myoclonus B, which is also bilateral and synchronous, is limited to the truncular musculature and to the proximal part of limbs. It never involves the eyelids and face. It never becomes generalized. Myoclonus C has a variable symptomatology and can be parcellar. The nervous structures originating the three types of myoclonus in the baboon are not identical. Myoclonus A is originated in the fronto-rolandic cortex, where a neuronal generator is triggered by visual inputs induced by photic stimulation. It appears mainly due to a dysfunction of the GABA system, because it is suppressed by GABA agonists and by benzodiazepines. On the contrary, it is facilitated by GABA antagonists. Myoclonus B has probably its origin in the lower brain stem (ponto-bulbar reticular formation) and is favored by cerebellar lesions. It appears mainly due to a dysfunction of the cholinergic system and is considerably facilitated by atropine. Myoclonus C can also have its origin in the lower brain stem but, contrary to myoclonus B, it can involve the cortex and thus can be accompanied by spikes-waves. The 3 types of myoclonus which are distinguished in the baboon have different relationships with epilepsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals

Chemical synaptic transmission is not necessary for epileptic seizures to persist in the baboon Papio papio.

The spread and persistence of epileptic seizures have generally been attributed to chemical synaptic interactions. Using ion-sensitive microelectrodes, we showed that in the allylglycine-treated photosensitive baboon, prolonged light-induced generalized seizures were accompanied by abnormally large decreases in the concentration of extracellular calcium ions, reaching values at which chemical synaptic transmission was certainly very reduced or blocked. This feature was observed in all cortical layers. Measurements of the concentration of extracellular potassium ions in the course of such light-induced seizures indicated that the observed low values of the concentration of calcium ions could not be ascribed to the occurrence of spreading depressions. These findings showed that nonsynaptic mechanisms play a prominent role in the persistence of epileptic seizures.

Animals

[Antiglobulin test using an immunoenzyme method].

An enzyme-linked antiglobulin test (ELAT) is described. All reagents are commercially available. The antiglobulin reagent is a monoclonal anti-IgG conjugated with alkaline phosphatase. The substrate (p-nitrophenylphosphate) is stable and innocuous. The procedure requires long incubations, particularly between red cells and the enzyme-conjugated antibody. However most of the time actively spent by the technician is consumed by washing procedures (LAV). These may be avoided by using density gradient centrifugation (CSG). ELAT is significantly more sensitive than agglutination, using either washing or gradient centrifugation (P = 0.002 and P = 0.0005, respectively). Moreover ELAT-CSG is significantly more sensitive than ELAT-LAV (P = 0.03). CSG yields better reproducibility and probably avoids some of the spontaneous elution of the primary and/or secondary antibody which may occur during washing.

Alkaline Phosphatase

Physostigmine antagonizes benzodiazepine-induced myoclonus in the baboon, Papio papio.

The antagonism of some benzodiazepine (Bz) actions by physostigmine was investigated in 4 Papio papio baboons. As a model of these actions, the myoclonus induced in this species by clonazepam i.m. administration was used. The baboon develops, 20-30 min after Bz i.m. injection, a non-epileptic myoclonus characterized by clinical symptomatology (jerks involving mainly the neck and the trunk bilaterally), by the absence of any correlative EEG discharge, and by its facilitation during movement. This Bz-induced myoclonus resembles the intention myoclonus of human patients, as seen for example after anoxia. In the present series, the effect of physostigmine i.v. injection on the frequency of clonazepam-induced myoclonus was tested. Physostigmine produces a rapid and total abolition of the myoclonus, and this effect lasts for a period which corresponds to the pharmacological activity of physostigmine. On the contrary, atropine i.v. injection considerably increases the amount of Bz-induced myoclonus. These results allow the existence of an anticholinergic action of benzodiazepines, reversed by physostigmine, and the theory that the myoclonus would be the consequence of a cholinergic system depression to be hypothesized.

Animals

Positron emission tomography in a case of experimental focal epilepsy in the baboon.

Repetitive limbic status epilepticus was produced in one baboon by intraamygdaloid microinjection of kainic acid. Brain metabolism was analysed by positron emission tomography (PET) after intravenous administration 18fluorodeoxyglucose (18FDG). In a control examination the distribution of 18FDG was symmetric in homologous parts of the brain. In contrast, during the epileptic state a restricted zone, the fronto-temporal region, showed increased 18FDG incorporation. This region corresponded to the side of kainic acid injection and to the limbic epileptogenic focus as demonstrated by EEG recording. The use of the non-invasive PET technique is suggested as an adjunct to classical EEG and clinical observation for the localization of an epileptic focus generating a status epilepticus.

Animals

The kinetics and displacement of [11C]flunitrazepam in the brain of the living baboon.

The distribution and kinetics of [11C]flunitrazepam in the brain were studied by positron emission tomography in the living baboon. Flunitrazepam was labelled on the methyl group with the 20 min positron emitter carbon 11. Fifteen to 25 mCi corresponding to 15-30 nmol were injected i.v. and sequential tomographic pictures of the brain were obtained. In some experiments, therapeutic doses of various benzodiazepines were injected i.v. subsequently in order to study the displacement of the radioactive ligand from brain structures. Lorazepam was shown to displace [11C]flunitrazepam from brain tissue, although other benzodiazepines (chlordiazepoxide, Ro 116896 and Ro 116893) led to a redistribution of the radioactive ligand in the body accompanied by an increase of brain radioactivity.

Animals

Cerebral and extracerebral blood volume in generalized seizures in the baboon Papio papio.

Relative variations of the cerebral and extracerebral blood volume (CBV) were measured continuously by a novel atraumatic method in baboons to explore the relationship between changes in the systemic circulation and in the cerebral (and extracerebral) vascular responses, before, during and after generalized seizures induced by photic stimulation. Major bursts of generalized spikes and waves are accompanied by an increase of the mean arterial pressure and of the cerebral blood volume and a decrease of the nasal blood volume. During the seizure discharge a substantial increase in CBV occurs, associated with a dramatic increase in arterial pressure. However, the greatest increase in CBV occurs after the peak mean arterial pressure. The results show that the CBV does not passively follow the blood pressure and demonstrate the dramatic responsiveness of the nasal region to seizure discharge.

Animals

Absence of seizure activity following focal cerebral injection of enkephalins in a primate.

Baboons (Papio papio) with photosensitive have been chronically prepared with guide cannulae and deep electrodes to study the effects of focal injections of opioids. In the hippocampus, amygdala and thalamus (centre median) 50--100 micrograms morphine, 20--100 micrograms Met-enkephalin or 2--10 micrograms FK 33,824 do not induce local or general electrographic or motor signs of epilepsy. The acute epileptogenic effect of morphine and enkephalins observed in rats is not a general phenomenon whereas the anticonvulsant action of opioids acting on mu-receptors is seen in rodents and primates.

Amygdala

[Modification of frontal and occipital cortical excitability provoked by trains of flashes in Papio papio (author's transl)].

The experimental conditions necessary for obtaining an evoked paroxysmal response from the frontal cortex were studied in the baboon Papio papio. The trigger stimulus was comprised of an isolated flash preceded by a train of intermittent light stimulation (SLI). Two conditions were necessary for the appearance of paroxysmal responses: a subconvulsant dose of DL-allylglycine had to be injected at least 3 h previous to recording, and a sufficient number of SLI trains had to be presented to the animal. The paroxysmal responses disappeared as soon as SLI trains were stopped. At the same time, modifications in the evoked occipital potential continue, although these do not become paroxysmal. These modifications appear either simultaneously with or previous to the paroxysmal frontal response.

Allylglycine