Low Voltage Fast Waves Research Articles

Absence-Like and Tonic Seizures in Aspartoacylase/Attractin Double-Mutant Mice

The Spontaneously Epileptic Rat (SER), a double-mutant for tremor and zitter mutations, shows spontaneous occurrences of absence-like and tonic seizures. Several lines of evidence suggest that the combined effect of Aspa and Atrn mutations is the most likely cause of the epileptic phenotype of the SER. To address this issue, we produced a new double-mutant mouse line carrying both homozygous Aspa-knockout and Atrn(mg-3J) mutant alleles. The Aspa/Atrn double-mutant mice exhibited absence-like and tonic seizures that were characterized by the appearance of 5-7 Hz spike-wave-like complexes and low voltage fast waves on EEGs. These results demonstrate directly that the simultaneous loss of the Aspa and Atrn gene functions causes epileptic seizures in the mouse and suggest that both Aspa and Atrn deficiencies might be responsible for epileptic seizures in the SER.

Micturition induced seizures: Ictal EEG and subtraction ictal SPECT findings

We report an 8-year-old girl with seizures induced by micturition. Her seizures were characterized by extension of upper extremities with preserved consciousness. Magnetic resonance imaging and interictal electroencephalograms were normal. Ictal electroencephalogram showed low voltage fast waves without clear focal features followed by frontal dominant rhythmic multiple spikes. Subtraction ictal single photon emission computed tomography revealed a significant increase in blood flow in the mesial frontal area.

The Wakayama epileptic rat (WER), a new mutant exhibiting tonic-clonic seizures and absence-like seizures.

A new mutant, the Wakayama epileptic rat (WER), exhibiting both spontaneous absence-like behavior and tonic-clonic convulsions, was identified in a colony of Wistar rats. To determine clear seizure characteristics of this mutant strain, we analyzed the mode of inheritance of the convulsion and observed patterns of electroencephalogram (EEG) during the seizures. F1 progeny were produced between the founder male and normal females of the same colony. Animals were monitored through the inbreeding course to analyze genetic control of epileptic behavior. EEGs were recorded using affected animals in the F3-4 and post F13 generations. After the F2 generation, affected rats spontaneously exhibited both absence-like immobile behavior and tonic-clonic convulsions. The absence-like seizures were characterized by motor arrest and head droop. The tonic-clonic convulsions began with neck and forelimb clonus, wild jumping/running, and opisthotonic posturing, and evolved to tonic, then clonic convulsions. Most convulsion onsets occurred between 25-70 days of age. Mating experiments revealed that 0%(0/18) of the animals in F1, 10%(3/26) in F2, 17%(1/6) in backcross progeny and 86% (100/116) in progeny of crosses between epileptic rats showed tonic-clonic convulsions. Ictal cortical EEGs were characterized by 4-6 (5.1 +/- 0.4, mean +/- SD) Hz spike-and-wave complexes in the absence-like seizures and by low-voltage fast waves in the tonic-clonic convulsions. This new mutant rat spontaneously exhibited both absence-like and tonic-clonic seizures. The tonic-clonic seizure was inherited as an autosomal recessive trait with 86% incidence. Thus, the new mutant rat may become a useful model for studying human inherited epilepsies.

Electroencephalographic studies of triterpene alcohol, a cerebral activator with a steroid compound, in rabbits and cats

The effects of triterpene alcohol, a cerebral activator with a steroid compound, on electroencephalographic (EEG) activity in rabbits and cats were examined in comparison with those of sterol and gammaoryzanol. In rabbits, doses less than 10 mg/kg (orally) of triterpene alcohol caused a slowing of spontaneous EEG activity of low-voltage fast waves for 40 to 50 minutes. In contrast, high doses (20 and 50 mg/kg orally) of the drug induced a dual arousal-resting-arousal EEG pattern but did not affect the EEG arousal response induced by sound stimulation. The animals exhibited an increased interest in their surroundings during the arousal period. The duration of the amygdaloid after-discharge elicited by electrical stimulation of the amygdaloid nucleus was enhanced by triterpene alcohol in rabbits. Gammaoryzanol was nearly as potent as triterpene alcohol, whereas the pharmacologic action of sterol was rather weak. In cats, triterpene alcohol also prolonged the duration of the amygdaloid after-discharge. These findings suggest that triterpene alcohol affects spontaneous EEG activity and markedly increases electrical activity in the limbic system, including the hypothalamus.

Tetraphasic actions of local anesthetics on central nervous system electrical activities in cats.

The effects of seven local anesthetics, mepivacaine, bupivacaine, etidocaine, dibucaine, prilocaine, procaine, and tetracaine, on the central nervous system (CNS) electrical activities were studied in five cats with each agent. Brain electrodes were implanted chronically in the cortex, amygdala, hippocampus, and midbrain reticular formation. The cortical, amygdala, and hippocampus electroencephalograms (EEGs), reticular multiunit activity (R-MUA), and heart rate were recorded. Drugs were administered intravenously with constant rates of equipotent doses until EEG seizures appeared. Effects of lidocaine, 1 mg.kg-1.min-1, were studied for comparison. The rates of infusion were: mepivacaine, 1 mg.kg-1.min-1; procaine, 4 mg.kg-1.min-1; bupivacaine and tetracaine, 0.25 mg.kg-1.min-1; etidocaine, 0.5 mg.kg-1.min-1; dibucaine, 0.15 mg.kg-1.min-1; and prilocaine, 3 mg.kg-1.min-1. The effects of 10-15 times higher rates of infusion were also studied in two cats with each drug. During the slow rates of infusion, a tetraphasic sequence of changes, common to all agents, was observed: the initial stage represented by diffuse EEG slowing and a suppression of the R-MUA; the second stage by low voltage fast wave EEG and an activation of the R-MUA; the third stage by reappearance of slow wave EEG and a suppression of the R-MUA; and the fourth stage by an epileptiform EEG and an activation of the R-MUA. These changes in EEG were not typical in some cats administered procaine, bupivacaine, prilocaine, and dibucaine. During the high rates of infusion, suppressive stages in the R-MUA were less dominant and activations dominated. High rates of infusion of mepivacaine produced sudden epileptic activities in EEG. Tetracaine, procaine, etidocaine, and bupivacaine in the high rates of infusion produced slow waves for a short period, prior to seizure activities in the EEG. Dibucaine or prilocaine in high rates of infusion could not produce seizure activities in the EEG, but slow waves and isoelectrical EEG, which were accompanied with idioventricular rhythm followed by ventricular fibrillation. All local anesthetics have similar tetraphasic CNS actions and whether the expression of CNS intoxication with subconvulsive doses is excitation or suppression may possibly be dependent on the brain drug level and its rate of increase.

Abnormal Excitability of Hippocampal CA3 Pyramidal Neurons of Spontaneously Epileptic Rats (SER), a Double Mutant

The spontaneously epileptic rat (SER: zi/zi, tm/tm), a double mutant, shows both tonic convulsions and absence-like seizures characterized by low-voltage fast waves and by 5-7 Hz spike and wave-like complexes in the cerebral cortical and hippocampal EEG, respectively. Characteristics of hippocampal CA3 pyramidal neurons were examined to determine whether these neurons are abnormally excitable. When a single stimulus was given to the mossy fiber, there was repetitive firing and a depolarization shift in neurons of mature SER (over 12 weeks old), in which epileptic seizures had fully developed. However, in young SER (7-8 weeks old) and littermates ( zi/zi, tm/+), which did not show any seizures, only a single spike was elicited with each single stimulation of the mossy fiber. Intracellular recording showed that the resting membrane potential was not significantly different among young and mature SER and littermates, but a long-lasting (100-200 ms) depolarizing shift accompanied by repetitive firing was observed following a single stimulation of the mossy fiber in half of the CA3 neurons of mature SER. Furthermore, the input impedance of the CA3 neurons in mature SER was lower than that in young SER and in littermates. These results indicate that SER hippocampal CA3 neurons become abnormally excitable in conjunction with the development of epileptic seizures.

Antiepileptic effects of CNK-602A, a novel thyrotropin-releasing hormone analog, on absence-like and tonic seizures of spontaneously epileptic rats

The effects of CNK-602A (N-[(6-methyl-5-oxo-3-thiomorpholiny) carbonyl]-L-histidyl-L-prolinamide), a novel thyrotropin-releasing hormone related analog, were investigated on absence-like seizure and tonic convulsion in the spontaneously epileptic rat (SER), which is a genetically defined double-mutant. When CNK-602A of 0.2–1 mg/kg was given intravenously to the animal, there were no changes in the background EEG except for an increase in low-voltage fast waves concomitant with behavioral altertness. However, CNK-602A suppressed absence-like seizure and tonic convulsion in a dose-dependent manner for over 1 h. These antiepileptic effects of CNK-602A on both seizures were antagonized by pretreatment with haloperidol (1 mg/kg, i.p.). It was found, using a brain in vivo microdialysis method, that CNK-602A at a dose of 1 mg/kg, which inhibits the seizures, increased the release of dopamine in the caudate nucleus. These results suggest that CNK-602A inhibits the seizures of SER in a similar manner to thyrotropin-releasing hormone (TRH), probably by increasing the release of dopamine in the central nervous system. In addition, the antiepileptic effects of CNK-602A were more potent and lasted longer than those of TRH.

Ontogeny of absence-like and tonic seizures in the spontaneously epileptic rat

The ontogeny of epileptic seizures in spontaneously epileptic rats (SER; zi/zi, tm/tm) was studied by examining behaviour and electroencephalogram (EEG) simultaneously. Weight gain and survival time were also studied. Compared with the control Kyo:Wistar rats, SER showed a much smaller increase in body weight. All male and female SER died before 20 and 18 weeks of age, respectively. Body tremor was observed at 2 weeks of age but disappeared after 11 weeks. Staggering gait appeared after 7 weeks of age, and intensified with age. Absence-like seizures characterized by paroxysmal appearance of 5-7 Hz spike-wave-like complexes were observed in the cortical or hippocampal EEG after 5 weeks of age, and tonic seizures with low voltage fast waves were observed after 6 weeks of age. All SER exhibited both absence-like and tonic seizures with high frequencies from 12 weeks of age. Differences with other spontaneous rat models of epilepsy and application methods for estimating seizure-inhibitory effects of anti-epileptic drugs are discussed.

新規抗不安薬・３ａα，４β，７β，７ａα‐Ｈｅｘａｈｙｄｒｏ‐２‐（４‐（４‐（２‐ｐｙｒｉｍｉｄｉｎｙｌ）‐１‐ｐｉｐｅｒａｚｉｎｙｌ）‐ｂｕｔｙｌ）‐４，７‐ｍｅｔｈａｎｏ‐１Ｈ‐ｉｓｏｉｎｄｏｌｅ‐１，３（２Ｈ）‐ｄｉｏｎｅ ｄｉｈｙｄｒｏｇｅｎ（ＳＭ‐３９９７）の中枢作用に関する脳波学的検索

Electroencephalographic (EEG) studies were performed to examine the effects of SM-3997 on the spontaneous EEG, EEG arousal responses, recruiting responses and hippocampal afterdischarges in rabbits and the spontaneous EEG in chronically electrode-implanted rats. In acute experiments using rabbits, SM-3997 at doses of 1-3 mg/kg, i.v., produced low-voltage fast waves in cortical EEG and slow waves with reduction of the amplitude in hippocampal EEG. The drug at doses of 1-3 mg/kg, i.v., dose-dependently inhibited the threshold stimulus voltages in EEG arousal responses induced by stimulation of the midbrain reticular formation and slightly inhibited the threshold in recruiting responses by stimulation of the centromedian nucleus of the thalamus. However, the cortical and hippocampal afterdischarges induced by hippocampal stimulation remained unaffected by SM-3997 at doses up to 3 mg/kg, i.v., while they were inhibited by diazepam of 1 mg/kg, i.v. In the study using rats in which electrodes were chronically implanted, SM-3997 at doses of 10-30 mg/kg, i.p., also produced low voltage fast waves in cortical EEG and slow waves of reduced amplitude in hippocampal EEG; and it simultaneously caused flat body posture. These results suggest that SM-3997 acts on both the cerebral cortex and hippocampus, inducing much more pronounced inhibition on the midbrain reticular formation-hippocampal system

Effects of antiepileptic drugs on absence-like and tonic seizures in the spontaneously epileptic rat, a double mutant rat.

Electroencephalographic (EEG) studies were performed to examine the effects of several antiepileptic drugs (AEDS) on absence-like and tonic seizures in the spontaneously epileptic rat (SER: zi(zi), tm/tm,), a double mutant rat, which was obtained by mating the tremor heterozygous animals (tm/ +) with the zitter homozygous animals (zi/zi), and to determine whether the seizures in the SER correspond to human absence and tonic seizures. Spontaneous EEG was continuously recorded from the frontal cortex and hippocampus using implanted electrodes. The SER showed paroxysmal and synchronized 5-7-Hz spike-wave-like complexes in both cortical and hippocampal EEG during the absence-like state, which was characterized by immobility and staring. The animal also exhibited tonic convulsion without external stimulation concomitant with low-voltage fast waves on cortical and hippocampal EEG. In some animals, sporadic low-amplitude spikes appeared in the low-voltage fast waves during tonic convulsion. the absence-like seizures were inhibited by trimethadione (100 mg/kg intraperitoneally, i.p.) and ethosuximide 100 mg/kg i.p.), whereas the tonic convulsion was not affected by these drugs. In contrast, phenytoin (20 mg/kg i.p.) inhibited the tonic seizures without affecting the absence-like seizures. Phenobarbital (10 mg/kg i.p.) and valproate (200 mg/kg i.p.) inhibited both seizures to a similar degree. These results suggest that the SER, with both absence-like and tonic seizures, is a useful model for evaluation of AEDS.

Etude electrophysiologique de la tianeptine, nouveau stimulant du recaptage de la serotonine possedant une activite antidepressive

Tianeptine is a clinically effective antidepressant, not chemically related to classical tricyclic compounds. Its mechanism of action preferentially involves central serotoninergic transmissions, by increasing uptake after acute and chronic administration in rat brain and platelets and in human platelets. We studied the effects of tianeptine on three currently used electrophysiological methods: Ro4-1284 induced PGO waves in the cat, neocortical EEG activity in the acute rat preparation and sleep-wakefulness modifications in chronically implanted rats. Density of Ro4-1284 induced PGO waves was reduced by tianeptine, the minimal effective dose being 2 mg.kg-1i.v. (ED50 = 2.9 mg.kg-1i.v.). In acute rat preparation, the low voltage fast waves basal EEG pattern was not modified by tianeptine in a dose range of 1.25 to 20 mg.kg-1i.p. Higher dosage (25 mg.kg-1i.p.) induced high amplitude episodes with few or no delta waves. Low doses which did not apparently modify acute EEG have been tested on sleep-wakefulness cycle in implanted rats. Tianeptine, after single administration, did not modify sleep states up to 2.5 mg.kg-1i.p. An increased wakefulness was observed during the first hour after 5-10 mg.kg-1i.p., afterwards sleep states returned to control values up to 12 h. A subsequent 12 h recording performed 24 h after treatment did not show any change compared to pretreatment baseline. After sub-chronic administration (2.5 mg.kg-1i.p./day, 9 days) no change was observed in sleepwake pattern during or after cessation of treatment. Tianeptine EEG profile is radically different from those usually induced by classical tricyclic antidepressants.

The maturation of the central auditory conduction in preterm infants until three months post term. IV. Composite group averages of the cortical auditory evoked responses (ACRs).

Composite group averages were constructed from cortical auditory evoked responses (ACRs), which are recorded sequentially at maximally 8 conceptional age levels in 5 groups of 49 preterm infants, with additional inclusion of the records of 16 prematures obtained at different conceptional age levels. The group averages for the 5 gestational age groups showed replicable waveforms at all conceptional age (CA) levels reflecting the intragroup stability of the ACR complex. From the earliest age levels, from 25 weeks CA on, ACR group averages can be obtained, containing relative low voltage fast waves and high voltage slow waves. The most outstanding developmental changes in the ACR complex are the waveform changes. Until about 36 weeks CA a premature waveform is found, followed by a transitional phase with low voltage noisy records. Finally the adult waveform is found in the measurements at three months after term date. The latency values of the group averages are determined by the waveform changes. Persistent amplitude differences are found for the slow late waves between the vertex and the central temporal derivations.

Electroencephalographic effects of 450191-S and its metabolites in rabbits with chronic electrode implants

Electroencephalographic (EEG) effects of 450191-S and its metabolites were investigated in unanesthetized rabbits with chronic electrode implants, and they were compared with those of nitrazepam and estazolam. 450191-S at doses of 0.1-0.5 mg/kg, i.v., induced a drowsy pattern of spontaneous EEG: high voltage slow waves and spindle bursts increased in the cortex and amygdala, while the hippocampal theta rhythm was desynchronized. In addition, low voltage fast waves appeared particularly in the cortical EEG. The EEG arousal response to auditory stimulation and to electric stimulation of the mesencephalic reticular formation, posterior hypothalamus and centromedian thalamus was markedly suppressed by 450191-S. The photic driving response elicited by a flash light in the visual cortex was significantly suppressed by 450191-S. 450191-S showed no significant effect on the recruiting response. The EEG effects of nitrazepam were qualitatively similar but less potent and shorter in duration of action than those of 450191-S. The effects of estazolam were approximately as potent as those of 450191-S, but its duration of action was much shorter than that of 450191-S. 450191-S was more potent than nitrazepam and approximately equipotent to estazolam in suppressing hippocampal and amygdaloid after-discharges. The EEG effects of M-1 and M-2 were similar to those of 450191-S in both qualitative and quantitative aspects. The effects of M-A were quantitatively similar but less potent and shorter in duration of action than those of 450191-S.

Naloxone reverses the hypnotic effect and the depressed baroreceptor reflex of halothane anaesthesia in the dog.

In order to evaluate the effect of an opioid antagonist on depressed intrinsic central vaso-motor drive (carotid sinus reflex) and high voltage slow delta waves in the EEG associated with halothane, naloxone was injected intravenously in a bolus of 100 or 200 micrograms.kg-1 on different days in the anaesthetized dog (0.64 Vol% halothane in oxygen). Only the 200 micrograms.kg-1 dose of naloxone reversed the halothane-induced depression of the blood pressure and heart rate response to clamping of both exteriorized common carotid arteries. The EEG changed from high voltage slow waves to low voltage fast waves, inducing a reduction of power in the delta band in spectral analysis. This effect was most pronounced during the 20th minute post naloxone injection. Naloxone did not reverse the halothane-related hypotension and bradycardia. Because of the late "cortical arousal" reaction during halothane-anaesthesia and the high dose necessary, naloxone appears to exert its action through a generalized increase in CNS excitation. An antagonisation of halothane-induced release of opiate-like peptides therefore is less likely.

Sleep-waking electrocorticographic rhythms in chronic cerveau isolé rats

Electrocorticograms (ECoGs) in blinded rats with a high mesencephalic transection (cerveau isolé) isolating both the raphe nuclei and locus coeruleus from the forebrain were continuously recorded for up to 21 postoperative days. After about 2 to 4 days, the low voltage fast wave recovered. Normal sleep-waking ECoG changes with a significant circadian rhythm reappeared in 4 to 9 days. The total amount and the average duration of the high voltage slow wave in chronic cerveau isolé rats after recovery were similar to those in intact rats. Bilateral lesions of the suprachiasmatic nucleus (SCN) abolished the circadian rhythm. These results suggest that in the forebrain rostral to the level of the locus coeruleus and raphe nuclei a mechanism inducing ECoG changes in transition from the slow wave sleep to waking and vice versa is localized.

E.E.G. ACTIVITY DURING HALOTHANE ANAESTHESIA IN MAN

The effects of i.v. administration of suxamethonium and noxious stimulation induced by skin incision on the e.e.g. were studied during halothane anaesthesia in man. These stimuli induced activation of the e.e.g. which was represented by either low-voltage fast waves or high-voltage slow waves. The low-voltage fast wave response was observed in adult patients while the high-voltage slow wave response was the predominant response in infants and children aged less than 8 yr. Suxamethonium induced the high-voltage slow wave response in 77% of cases; skin incision in 88%. The e.e.g. of four infants aged less than 60 days did not show activation with either stimulus. Both types of e.e.g. activation were associated with an increase in heart rate, increase in arterial pressure and pupillary dilatation. The possible mechanisms involved in the production of activation of e.e.g. by i.v. administration of suxamethonium are discussed.

Changes in electroencephalogram of the rat following olfactory bulbectomy.

The changes in electrical activities following olfactory bulbectomy were investigated in rats with chronically implanted electrodes, in comparison with those induced by septal lesions. Electroencephalogram (EEG) of the amygdala changed to low voltage fast waves immediately after bilateral olfactory bulbectomy, while EEG of the neocortex gradually showed an arousal pattern consisted of low voltage fast waves, and hippocampal theta waves were markedly synchronized during the period of a week or so after bulbectomy accompanied with the appearance of characteristic hyperemotionality. No change was observed in EEG of the septum, hypothalamus or the midbrain reticular formation. Following unilateral olfactory bulbectomy, no behavioral changes occurred, but EEG of the ipsilateral amygdala showed low voltage fast activity without causing any EEG changes in other brain structures. Bilateral septal lesions immediately caused hyperreactivity in rats which gradually disappeared during the course of a week or two after the surgery. The hippocampal theta activity completely disappeared and EEG turned to low voltage fast waves immediately after septal lesions, but no significant EEG change was observed in the amygdala or the neocortex. This change in hippocampal EEG continued for a long time even after hyperreactivity disappeared.

Hallucinatory and Delusional States in Connection with Blood Pressure and EEG

Twenty-two patients who had low blood pressure with hallucinatory and delusional states were examined. Nineteen cases showed low voltage fast waves in EEG. By treatment with haloperidol the symptoms as well as the blood pressure and EEG showed improvement. From the above findings, the hallucinatory and delusional states observed in this study may have a close connection with dysfunction of the lower brain or disharmony of function between the upper and the lower brains.

Cocaine and pseudococaine: Comparative effects on electrical after-discharge in the limbic system of cats

The effects of cocaine and its dextroisomer pseudococaine on electrical after-discharge (AD) evoked by electrical stimulation of the hippocampus or amygdala were studied in cats with electrodes implanted in the brain. Intravenous injection of cocaine (2.0 to 4.0 mg/kg doses) produced a suppressive effect on the AD while producing low-voltage fast waves (LVFWs) in the electrical activities of the brain (EEG) associated with behavioral excitation. In contrast, pseudococaine at the same dose as cocaine failed to show a significant suppressive effect on the AD except at high doses (5.0 mg/kg). Pseudococaine produced high-voltage slow waves (HVSWs) in the EEG associated with behavioral depression. A linear dose-response relationship was observed for the suppressive effect of cocaine on the AD. The results suggested that the limbic system may be involved as a primary site of action of cocaine in the central nervous system (CNS).

Comparison of the convulsant effects of cocaine and pseudococaine in the rhesus monkey

The convulsant effects of cocaine and its C 2 -epimer, pseudococaine on EEG, respiration, heart rate and behavior were studied in the rhesus monkeys with electrodes implanted in the brain. Intravenous injections of cocaine (3.0 to 8.0 mg/kg) and pseudococaine (3.0 to 7.0 mg/kg) in the animals produced a similar pattern of clonic convulsions accompanied by marked increases in the heart and respiratory rates with mydriasis and excessive salivation. However, both isomers showed different effects on the EEG and animal's behavior following convulsions; e.g., the cocaine-induced convulsions were followed by low-voltage fast waves in the EEGs associated with behavioral hyperexcitation, while pseudococaine-induced convulsions were followed by high-voltage slow waves associated with behavioral depression and drowsiness with intermittent sleep. Pseudococaine was more potent than cocaine in producing convulsions in the same monkeys. The durations of convulsions produced by these drugs were dose-dependent.