Visualisation of 11C-flunitrazepam displacement in the brain of the live baboon.
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Biomedical subjects
Publications and source records attributed to R Naquet.
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The method of labelling red cells with technetium-99m was used to measured regional blood volume auring different types of epileptic seizures induced in the Baboon Papio papio. During seizures the cerebral blood volume increases and there is simultaneously a decrease of blood volume in nasal and hepatic regions, and a transitory increase of blood volume in the forepaws.
The effects of intracerebroventricular (i.c.v.) or systemic injections of Met- or Leu-enkephalin, beta-endorphin, FK 33.824 (D-Ala2, MePhe4, Met(O5)-ol-enkephalin) and of morphine and naloxone have been studied in baboons, Papio papio, which spontaneously show photically induced epileptic responses. Animals were chronically implanted with epidural or deep recording electrodes and a cannula in one lateral ventricle, and tested whilst seated in a primate chair. In some animals the natural syndrome was enhanced by the prior administration of DL-allylglycine, 100--200 mg/kg, i.v. Met- or Leu-enkephalin, 1--10 mg, i.c.v., did not lead to any manifest focal or generalized seizure discharges. Nor did it lead to any consistent enhancement or reduction of photically induced myoclonic responses (as tested 5--10 min after injection). beta-Endorphin, 0.1--0.5 mg, i.c.v., did not enhance or impair photically induced myoclonic responses. FK 33.824, 0.1--0.5 mg, i.c.v., depressed respiration and slowed EEG background rhythms for 9--15 h. This was associated with a loss of myoclonic responses to photic stimulation. These effects were reversed for 20--40 min following the injection of naloxone, 1 mg/kg i.m. A depression of respiration and a slowing of EEG rhythms was seen beginning 5--20 min after FK 33.824, 2 or 4 mg/kg, i.v. The higher dose also abolished photically induced myoclonic responses. Naloxone, 1 mg/kg, definitively reversed these effects. Morphine, 5--10 mg i.c.v., tended to increase the latency to onset of generalized myoclonus during photic stimulation. Myoclonic responses were delayed or diminished after morphine, 5 mg/kg, i.m. Naloxone, 1--2 mg/kg i.m., reversed this effect. Naloxone, 0.2--5.0 mg/kg i.m., alone, did not significantly modify photically induced myoclonus, either in animals of low or high initial responsiveness, or in those pretreated with allylglycine.
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The effects of the intravenous or intracerebroventricular injection of the stereoisomers, and the racemic mixture, of allylglycine (2-amino-pent-4-enoic acid) have been studied in baboons, Papio papio, with photosensitive epilepsy. Enhancement of the natural syndrome of photosensitivy epilepsy is seen 1-12 h (maximally at 3-8 h) after L-allyglycine, 100 mg/kg, intravenously, or D,L-allyglycine, 200 mg/kg, intravenously. Such enhancement is seen with a slower onset, and to a lesser, and more variable, extent after D-allyglycine, 500-750 mg/kg, intravenously. Brief focal or generalised seizures occurred (in the absence of intermittent photic stimulation) after L-allyglycine, 150-200 mg/kg, intravenously. This effect is similar to that previously observed after D,L-allyglycine, 300-400 mg/kg. D-Allyglycine, 780 mg/kg, intravenously produced episodes of vertical nystagmus with increased extensor motor tone, but no 'spontaneous' seizures. Intracerebroventricular injection of L-allylglycine, D-allyglycine or D,L-allyglycine, 100 mg in 1 ml saline, did not modify the natural syndrome of photosensitive epilepsy. D-Allylglycine, or D,L-allyglycine, 100 mg intracerebroventricularly, after 1-2 h gave rise to a syndrome with vomiting, sustained vertical nystagmus, and intermittent extensor spasms. The results are interpreted in terms of regional differences in the metabolism of the two isomers to active compounds that can inhibit glutamic acid decarboxylase. D-Allylglycine is active only at the brain stem and cerebellum because D-amino acid oxidase is largely confined to these brain areas.
The benzodiazepine receptor in the cortex of 1 spontaneously epileptic baboon exhibited an increased rate of thermal inactivation at 65 degrees C when compared with those from 3 other baboons. In other respects (receptor concentration, affinities for flunitrazepam and diazepam, and response to changing pH), the benzodiazepine receptor from this animal was very similar to the receptors in the cortex of 3 other baboons. The 3H-QNB (muscarinic) and 3H-naloxone (opiate) binding sites in the brain of all 4 baboons appeared very similar with respect to all parameters studied (thermal stability, concentration, regional distribution, and affinities for respective ligands). An endogenous factor stabilizing the benzodiazepine receptor could be lacking in the spontaneously epileptic baboon.
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The Valsalva manoeuvre was performed by 2 groups of young healthy male subjects: novice divers and professional divers. The electrophysiological features of this manoeuvre are summarized and the results of the test are correlated with subject age, motivation and FEV1/VC coefficient (forced expiratory volume sec/vital capacity). Positive test results (fainting caused by the Valsalva manoeuvre) increased with subject motivation (novice divers), FEV1/VC coefficient and decreasing subject age. The various hypotheses proposed to account for fainting caused by the Valsalva manoeuvre are discussed with respect to these data. The implications of Valsalva positivity in young divers are discussed.
Two vermisectomized photosensitive baboons exhibited two different types of myoclonus, one induced by intermittent light stimulation (ILS) and the other occuring "spontaneously". The characteristics of these two types of myoclonus are described from a clinical and from an ECoG point of view. Myoclonus induced by ILS (ML) started at the eyelids and secondarily invaded the face and body; it was always preceded by frontorolandic spike-waves or polyspike-waves. The "spontaneous" myoclonus which followed vermisectomy (MV) was "massive", but involved firstly the trunk and secondarily the face and limbs; no ECoG paraoxysm accompanied this myoclonus, but we observed a parietal evoked potential of small amplitude, 10--15 msec after its onset. If MLs can be considered as consequences of the fronto-rolandic paroxysmal discharges, MVs seem to originate in the brain stem but appear similar to action myoclonus. This experimental situation showing two types of myoclonus resembles human hereditary degenerative syndromes (dyssynergic cerebellar myoclonus, progressive myoclonic epilepsy), without being exactly comparable. The conditions in which MVs were seen and their modifications during sleep and by different drugs are described. The relationships between MVs and MLs and myoclonic epilepsy are discussed.
Unilateral or bilateral electrographic temporal discharges at 5 Hz were analyzed in relation to their morphological characteristics, their topography, and their evolution in II subjects. The clinical context, in which there was no evidence of epileptic disorder, was also analyzed. These discharges were compared to other infraclinical critical phenomena reported in the literature, and related to similar manifestations described by the Gibbs "school" as "Psychomotor variant type of discharge", or by Hughes group as "Rhythmic mid Temporal discharges".
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Recording electrodes were implanted stereotaxically in limbic and thalamic structures and the mesencephalic reticular formation in twelve cats. The animals were submitted to daily stimulation of the left amygdaloid nucleus following the technique for the kindling procedure, always combined with 5 h 30 min post-stimulation monitoring. After about 18 days, generalized convulsive activity was established. The following results concerning the quantitative evolution of spontaneously occurring interictal spikes were obtained. Amygdaloid nuclei, the hippocampus and the thalamic nucleus ventralis lateralis (VL) demonstrated an increase of discharge activity during the kindling procedure, following by a significant decrease after convulsions had been elicited. Thalamic nucleus centrum medianum (CM) was the only recording site investigated where the amount of interictal discharge increased and remained at a high level even after generalized convulsions had been established. Fourier analysis of slow oscillations in discharge generation yielded two main types of significant periodicity. A 165 min oscillation could be detected in all structures tested except reticular formation, which developed a 110 min cycle shared only with the thalamic CM. Significant correlations in spike activity were obtained from various structures. Stimulated amygdala seemed to have alternating relations with thalamic CM and VL, whereas stimultaneous oscillations excisted between MRF and CM. The occurrence of high voltage spikes in both contralateral and ipsilateral amygdalae was shown to be significantly correlated.
The effect of an antiepileptic drug, valproic acid (VPA), on an experimental form of epilepsy, the kindling phenomenon, is described. In cat, 50 mg/kg i.p. per day is sufficient to block the progressive establishment of generalized seizures produced normally by repetitive electrical stimulation of the amygdala. However, a focal afterdischarge persists during the entire treatment. Higher doses (75-150 mg/kg) are necessary to protect the animal against the generalized tonic-clonic seizure when the kindling phenomenon is established. These effects and the action of barbiturates, which was also tested, seem to attribute to VPA a complex role in the mechanism of this action.
This review deals with the common E.E.G. characteristics of dysmetabolic encephalopathies and described the particular features of hepatic, respiratory and renal encephalopathies, as well as those resulting from a disturbance in carbohydrate, water and electrolyte metabolism. These now classical data are compared with the principal electroclinical appearances seen during parenteral alimentation : slow, ample wases, non-reactive, associated with a calm coma; overall depression of basal rhythm, with excessive myogram activity and corresponding to paroxysms of muscular hypertonia seen during the coma.
Effects of different types of epileptic seizure on the sleep organization of baboon were studied through 12 h polygraphic recordings. Photically induced myoclonic jerking did not modify sleep organization. Photically induced genalized convulsions produced an increase of the waking stage (AWA) and reduction of REM stage. Pentetrazol-induced generalized convulsions not only increased AWA and reduced REM, but also elicited various modifications of stages I, II and III. Daily generalized convulsions induced by light or pentetrazol over 5 days demonstrated no rebound of REM.
Averaged evoked responses (AER) to light flashes were recorded in baboons (Papio papio) during wakefulness, slow-wave sleep and rapid eye movement (REM) periods, at the visual cortex, retrocalcarine sulcus, optic tract (OT), lateral geniculate (LG) and pulvinar. Waking AERs were composed: in the OT, of a negative, low amplitude wave at 13.3 msec (I), a high amplitude wave at 34.8 msec (II), a negative wave at 72 msec (III) and a late component at 151 msec; in the LG, a small positive wave (II) with a peak latency of 40 msec, a high amplitude negative wave (III) with a latency of 70 msec and a late component; in the pulvinar of two low amplitude short latency waves (I and II), respectively negative and positive at 25 msec and 40 msec, then a high amplitude negative wave (III) at 75 msec and a late component; in the retrocalcarine sulcus 3 positive waves (I, II and III) were recorded at 25, 45 and 100 msec and a late component; in the visual cortex, 3 low amplitude negative waves (II, III and IV at 40, 50 and 54 msec, then a positive wave at 80 msec and some late components. In slow-wave sleep, AERs did not change in the OT, but in the LG and pulvinar, they showed an increase in the amplitude of wave II from stage 1 to stage 3. At the cortical level, early waves (II for the retrocalcarine sulcus, II and IV for the visual cortex) presented a marked increase in amplitude during stages 2 and 3, but only a slight increase for stage 1. Peak latency increase of each wave in cortical and subcortical AERs was seen during slow-wave sleep. REM AERs resembled, in amplitude and peak latency, those recorded in the LG and pulvinar during wakefulness; in the visual cortex and retrocalcarine sulcus, they were similar to those obtained during wakefulness and stage 1. In conclusion, a different evoked response was found between visual cortex and deep structures (except for the OT): firstly, during slow-wave sleep (the AERs showed a difference for stage 1 between the visual cortex or the retrocalcarine sulcus and the LG or the pulvinar), secondly, in REM (on the cortex, REM AERs looked like wakefulness and stage 1 responses); on the contrary, in the LG and pulvinar, REM AERs were similar only to those recorded during waking. Finally, it can be said that for Papio papio the differentiation and structural responses between the various stages of sleep (particularly light sleep and REM) were greater in the cortex than in the thalamic structures.
Facial nerve neurectomy were performed in the baboon (Papio papio). Histochemical investigations showed usual criteria of such lesions. Therefore a loose of glycogene within the Type I muscular fibers was observed in animals with a former facial spasm.