Local cerebral metabolism during enflurane anesthesia: Identification of epileptogenic foci

doi:10.1016/0013-4694(79)90217-7

Electroencephalography and Clinical Neurophysiology

Volume 47, Issue 2, August 1979, Pages 153-162

https://doi.org/10.1016/0013-4694(79)90217-7 Get rights and content

Abstract

Electrocorticographic (ECoG) and depth recordings have previously demonstrated the epileptogenic nature of surgical concentrations of the volatile anesthetic enflurane. We contrasted ECoG activity with local cerebral glucose uptake ([¹⁴C]2-deoxyglucose autoradiography) in 23 brain structures in order to identify the epileptogenic foci. Autoradiograms were obtained from sectioned rat brain following a 30 min period of steady-state anesthesia at 1, 1.5, or 2 MAC (minimum alveolar concentration) enflurane.

Pseudo-epileptiform ECoGs were obtained at 1 MAC where bursts of slow waves and sharp waves were evoked by peripheral sensory stimulation. At 1.5 MAC, the ECoG displayed frank, spontaneous epileptiform activity with large amplitude spike-wave complexes; repetitive auditory stimulation occasionally precipitated grand-mal seizures. At 2 MAC, spike complexes were less frequent and could not be repetitively driven.

At 1 MAC enflurane, regional cerebral metabolism was generally depressed approximately 14% from the awake controls. However, metabolism in the dentate gyrus of the hippocampus and other subcortical structures in the limbic brain was increased. At 1.5 MAC this dichotomy in local cerebral metabolic rate was maximal; we observed increased metabolism in the hippocampus, habenula, habenulo-interpeduncular tract and interpeduncular nucleus and pineal. Metabolism in all other structures was significantly depressed (P < 0.05) compared to awake values. At 2 MAC, metabolism was decreased in all structures.

We conclude that the low seizure threshold hippocampus and related structures associated with the limbic system and its pathways are the epileptogenic foci for seizures induced with enflurane in the rat. At 1.5 MAC, epileptiform activity spreads throughout the visceral brain when seizure threshold is at a minimum.

Résumé

Des enregistrements électrocorticographiques (ECoG) et profonds ont antérieurement montré la nature épileptogène de concentrations chirurgicales d'enflurane anesthésique volatile. L'activité ECoG a été contrastée par renforcement cérébral local de glucose (autoradiographie [¹⁴C]2-déoxyglucose) dans 23 structures cérébrales afin d'identifier le foyer épileptogène. Les autoradiogrammes sont obtenus chez des rats dont le cerveau a été sectionné après une période de 30 min d'anesthésie stable à 1, 1,5, ou 2 MAC (concentration alvéolaire minimale) d'enflurane.

Des ECoGs pseudo-épileptiformes sont obtenus à 1 MAC, tandis que des bouffées d'ondes lentes et d'ondes pointues sont évoquées par stimulation sensorielle périphérique. A 1,5 MAC, l'ECoG montre une activité épileptiforme franche et spontanée avec des complexes pointe-ondes de grande amplitude; la stimulation auditive répétitive précipite occasionnellement des crises grandmal. A 2 MAC, les complexes de pointes sont moins fréquents et ne peuvent pas être entraînés de façon répétitive.

A 1 MAC d'enflurane, le métabolisme cérébral régional est généralement déprimé, d'environ 14% par rapport aux contrôles de veille. Cependant, le métabolisme est augmenté au niveau du gyrus dentelé de l'hippocampe et d'autres structures sous-corticales du cerveau limbique. A 1 MAC, cette dichotomie du taux métabolique cérébral local est maximale; le métabolisme est accru dans l'hippocampe, l'habenula, le tractus habenulo-interpédonculaire et le noyau interpédonculaire et pinéal. Le métabolisme dans toutes les autres structures est significativement déprimé ( $P < a ̀ 0,05$ ) par comparaison aux valeurs de la veille. A 2 MAC, le métabolisme est diminué dans toutes les structures.

Les auteurs concluent que l'hippocampe et les structures associées au système limbique et ses voies constituent du fait de l'abaissement du seuil critique, le foyer épileptogène des crises induites par enflurane chez le rat. A 1,5 MAC, l'activité épileptiforme diffuse sur tout le cerveau vicéral quand le seuil critique est à son minimum.

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Citation Excerpt :
Moreover, sevoflurane (4%) was without effect even against this more moderate insult. Since volatile anaesthetics reduce cerebral metabolic rate [14,15] and this effect might thereby mask any preservation of cerebral metabolism, we investigated any effects persisting after anaesthetic washout. Thus, in one group of slices, the anaesthetic (sevoflurane 4%) was discontinued for the last 30 min prior to TTC staining (60 min total recovery).
Previous studies using a rat brain slice model of cerebral ‘ischaemia’ (hypoxia and hypoglycaemia) have suggested that volatile anaesthetics may have cerebroprotective potential. In this study, we tested the cerebroprotective profile of four volatile anaesthetics in this model by two independent means: voltammetric measurement of ‘ischaemia’-induced dopamine (DA) release and post-‘ischaemic’ tissue staining with 2,3,5-triphenyltetrazolium chloride (TTC). ‘Ischaemia’ caused a characteristic pattern of DA release. Halothane, isoflurane and enflurane did not affect the time from onset of ‘ischaemia’ to the initiation of DA release. However, all three volatile agents significantly increased (P<0.01, P<0.05, P<0.001, respectively) the time taken for ‘ischaemia’-induced DA release to reach maximum and reduced the rate of DA release. Enflurane, unlike halothane or isoflurane, reduced the maximal extracellular DA concentration induced by ‘ischaemia’ (P<0.01). The effects of sevoflurane were inconsistent. At the higher concentrations used, the volatile anaesthetics frequently changed the character of DA release from monophasic to biphasic, an effect only previously seen in this model with Na⁺ channel blockers. ‘Ischaemia’ also diminished the subsequent level of tissue staining with TTC. When the effects of the volatile agents were analysed by TTC staining, only enflurane showed any cerebroprotective effects and these were limited to the striatum (P<0.01). High concentrations of halothane, isoflurane and enflurane appeared to have some ‘toxic’ effects, reducing TTC staining in control slices. In summary, we do not find any consistent evidence that volatile anaesthetics are cerebroprotective in this model.
Local cerebral glucose utilization in the postictal phase of amygdaloid kindled rats
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Local cerebral glucose utilization was measured by means of the quantitative autoradiographic 2-[¹⁴C]deoxyglucose method during the postictal phase of various seizure stages of amygdaloid kindling in conscious rats. The partially kindled animals exhibited a partial seizure such as chewing and/or head nodding, and the fully kindled animals, a generalized tonic-clonic convulsion. The control animals were implanted with an electrode, but not electrically stimulated. Cerebral glucose utilization of the fully kindled animals was deeply depressed in the postictal phase as compared to the control, and that of the partially kindled animals was moderately decreased. The side-to-side differences of cerebral glucose utilization were observed only in the partially kindled group in which glucose utilization was more depressed on the side of stimulation. Among the structures with depressed glucose utilization, only one structure, the interpeduncular nucleus, showed a relative increase in glucose utilization during the postictal phase of the kindled groups. As the postictal phase has been considered as a period of inhibition, these results may indicate that the neural networks linking the interpeduncular nucleus play an active role in the mechanisms of termination of a seizure and postictal refractoriness.
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The [1-¹⁴C]2-deoxyglucose technique was employed for an evaluation of the regional pattern of alteration of brain metabolism induced by the anxiolytics phenobarbital (which is described in small doses as anxiolytic agent) and meprobamate. Their effects were compared with those produced by the anxiolytic benzodiazepine diazepam which we have described in a previous study. In low doses, both meprobamate (30 mg/kg i.v.) and phenobarbital (5 mg/kg i.v.) elicited a regional pattern of changes similar to those seen with diazepam. Thus, the local cerebral glucose utilization (LCGU) of the mammillary nuclei, the lateral and ventral thalamic nuclei, the anterior thalamic nuclei and the geniculate nuclei was significantly decreased. A doubling of the dose (meprobamate 60 mg/kg i.v.; phenobarbital 10 mg/kg i.v.), however, resulted in a decrement in LCGU in virtually every brain region examined. Further, at this higher dose, phenobarbital significantly increased LCGU in the interpeduncular nucleus. These data demonstrate that both meprobamate and phenobarbital, in moderate doses induce selective alterations in LCGU in particular brain regions with the pattern of changes similar to that induced by diazepam. The structures affected may be of general importance for the expression of the anxiolytic actions of each of those classes of minor tranquilizers in clinical use.
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Local changes in cerebral 2-deoxyglucose uptake during alphaxalone anaesthesia with special reference to the Habenulo-Interpeduncular system
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The effects of the steroid anaesthetic Althesin (alphaxalone plus alphadolone acetate) on regional cerebral metabolism was studied in female rats. [¹⁴C]2-Deoxyglucose (2-DG) uptake was measured in 19 discrete anatomical areas by quantitative autoradiography. Under Althesin anaesthesia metabolic activity, relative to the corpus callosum (rma), was significantly (24–46%) increased in the locus coeruleus, medial (but not lateral) habenula (Hb) and interpeduncular nucleus (IPN). The Hb-IPN tract, not discernible in autoradiograms from conscious rats, became readily apparent in films from anaesthetized rats. However, the increased metabolic activity of this pathway was not associated with a significant change in the tissue concentrations of substance P in either the Hb or IPN. In sensorimotor and visual cortex, caudate nucleus, thalamic nuclei and the medial geniculate body rma was significantly (26–38%) depressed. Metabolic activity in the other 8 areas measured was unaffected by Althesin. Destruction of the stria medullaris input to the habenulae prevented the Althesin-induced increase in 2-DG uptake by the MHb and LHb.

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^☆: Supported by the Medical Research Service of the Veterans Administration.

^∗: The authors thank Messrs. Kenneth Ray, Robert Kohlenberger and Martin Ingvar for their expert technical assistance, and Ohio Medical Products for Ēthrane^® and vaporizer.

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Local cerebral metabolism during enflurane anesthesia: Identification of epileptogenic fociMétabolisme cérébral local au cours de l'anesthésie par enflurane: identification d'un foyer épileptogène☆

Abstract

Résumé

Electroenceph. clin. Neuophysiol.

Electroenceph. clin. Neuophysiol.

Neuroscience

Epileptogenicity of enflurane and isoflurane in man and cats: selective effects of PaCO2 on intersuppression activity and seizure duration

Visual and auditory evoked responses during penicillin-induced generalized spike and wave activity in cats

Epilepsia

Relationship of pre- and post-anesthetic EEG abnormalities to enflurane-induced seizure activity

Anesth. Analg. Curr. Res.

Cardiovascular effects of controlled ventilation in man

Anesth. Analg. Curr. Res.

Metabolic anatomy of focal motor seizures

Arch. Neurol. (Chic.)

Penicillin induced interictal discharges from the cat hippocampus. I. Characteristics and topographical features

J. Neurophysiol.

Anatomical correlates of electrical and behavioral events related to amygdaloid kindling

Ann. Neurol.