Constrictive pericarditis--do we need a complete decortication?

A capacitance sensor which detects vibrations caused by the movements of animals can be used for measuring automatically the clonic convulsions induced by chemical convulsants. This knowledge has been utilized to devise an instrument which has satisfactorily measured the clonic convulsions induced by picrotoxin in rats.     

Biotransformation of 17-alkylsteroids in the equine: gas chromatographic-mass spectral identification of ten intermediate metabolites of methyltestosterone

Parenterally administered domoic acid, a structural analog of the excitatory amino acids glutamic acid and kainic acid, has specific effects on brain histology in rats, as measured using different anatomic markers. Domoic acid-induced convulsions affects limbic structures such as hippocampus and entorhinal cortex, and different anatomic markers can detect these neurotoxic effects to varying degrees. Here we report effects of domoic acid administration on quantitative indicators of brain metabolism and gliosis. Domoic acid, 2.25 mg/kg i.p., caused stereotyped behavior and convulsions in approximately 60% of rats which received it. Six to eight days after domoic acid or vehicle administration, the animals were processed to measure regional brain incorporation of the long-chain fatty acids [1-(14)C]arachidonic acid ([14C]AA) and [9,10-(3)H]palmitic acid ([3H]PA), or regional cerebral glucose utilization (rCMRglc) using 2-[1-(14)C]deoxy-D-glucose, by quantitative autoradiography. Others rats were processed to measure brain glial fibrillary acidic protein (GFAP) by enzyme-linked immunosorbent assay. Domoic acid increased GFAP in the anterior portion of cerebral cortex, the caudate putamen and thalamus compared with vehicle. However, in rats that convulsed after domoic acid GFAP was significantly increased throughout the cerebral cortex, as well as in the hippocampus, septum, caudate putamen, and thalamus. Domoic acid, in the absence of convulsions, decreased relative [14C]AA incorporation in the claustrum and pyramidal cell layer of the hippocampus compared with vehicle-injected controls. In the presence of convulsions, relative [14C]AA incorporation was decreased in hippocampus regions CA1 and CA2. Uptake of [3H]PA into brain was unaffected. Relative rCMRglc decreased in entorhinal cortex following domoic acid administration with or without convulsions. These results suggest that acute domoic acid exposure affects discrete brain circuits by inducing convulsions, and that domoic acid-induced convulsions cause chronic effects on brain function that are reflected in altered fatty acid metabolism and gliosis.     

Pharmacological analysis of local anaesthetic tolycaine-induced convulsions by modification of monoamines in rat brain

The effects of a local anaesthetic, tolycaine, on brain monoamine levels were investigated during the convulsive process in rats. The influence of central monoamine modifications on tolycaine-induced convulsions was also examined. Tolycaine (140 mg/kg, intraperitoneally) produced a significant elevation of noradrenaline and 5-hydroxytryptamine levels in all brain regions in the convulsive state from the levels in the non-convulsive state. Their levels returned to normal during the postconvulsive state. Dopamine levels were depleted in the cerebral cortex, the striatum, and the ponsmedulla oblongata during the convulsive process and increased in the cerebellum. Pretreatment with alpha-methyl-p-tyrosine, which depletes brain catecholamine, suppresses the tolycaine-induced convulsions, as shown by a decrease in the incidence; L-3,4-dihydroxyphenylalanine and bis-(1-methyl-4-homopiperazinyl-thiocarbonyl)-disulfide, which increase brain catecholamine, intensified the convulsions, as shown by shortening of the latency and increase in the mortality. Antagonists of beta-adrenergic and dopamine receptors, such as propranolol, chlorpromazine and pimozide, markedly suppressed the convulsions, but an antagonist of alpha-adrenergic receptor, phenoxybenzamine, had no effect. Furthermore, 5-hydroxytryptophan, which increases brain 5-hydroxytryptamine, suppressed the convulsions, and DL-p-chlorophenylalanine, which depletes brain 5-hydroxytryptamine, intensified them. Antagonists of 5-hydroxytryptamine receptor, methysergide and methiothepin, suppressed the convulsions. These results suggest that brain noradrenaline and 5-hydroxytryptamine are major regulators in the tolycaine-induced convulsive process and that central catecholaminergic neurones act in a stimulatory way on the tolycaine-induced convulsions, while serotonergic neurones act suppressively.     

Influence of ZnCl2 pretreatment on behavioral and histological responses to kainic acid in rats

Kainic acid evokes behavioral convulsions and causes lesions in hippocampal pyramidal cell layers in rats. The effects of ZnCl2 pretreatments on these events were examined. Rats were given ZnCl2 (35 mg/kg, subcutaneously (s.c.)) 15 min prior to kainic acid administration (12 mg/kg, intraperitoneally (i.p.)). Another group of animals was given an additional dose of ZnCl2 (35 mg/kg, i.p.) 24 h prior to the s.c. ZnCl2 and i.p. kainic acid. All rats that received kainic acid, whether saline controls or ZnCl2 pretreated, experienced wet dog shakes (WDS) and convulsions. No significant differences were seen between groups in number or latency of WDS or convulsions. Two days after behavioral data were collected, the brains were perfused and the extent of lesioning among hippocampal CA1 and CA3 pyramidal cells was quantified. A single dose of ZnCl2 had either no effect or a slight protective effect on cell lesioning induced by kainic acid. However, lesioning was more pronounced in animals treated twice with zinc. It is concluded that zinc, co-administered with kainic acid, augments kainate cytotoxicity when the dose and timing of zinc exposure are within a critical period.     

Risk factors for preeclampsia, abruptio placentae, and adverse neonatal outcomes among women with chronic hypertension. National Institute of Child Health and Human Development Network of Maternal-Fetal Medicine Units

The study comprised 80 children aged 6 to 9 years with a history of febrile convulsions. A neurological examination, an interview to assess psychiatric anomalies, and a series of neuropsychological tests were performed on patients with previous febrile convulsions and on matched healthy controls. Children with non-febrile seizures or CNS infections were excluded. Recurrence of febrile seizures in the study group was 41% (N=33), 18 children (22%) had prolonged febrile convulsions, six (7.5%) patients and two controls showed discrete neurological abnormalities. Behavioral anomalies were exhibited by 22% of the patients and 6% of the healthy children. The neuropsychological test results did not demonstrate significant differences between the children with febrile convulsions and the healthy controls. However, in children with prolonged febrile convulsions, non-verbal intelligence was found to be significantly lower as compared with children with simple febrile seizures and with controls. None of the other parameters tested yielded any differences between patients and controls. Children with multiple recurrences of febrile convulsions performed poorer in all tests when compared with children with only one febrile seizure or with controls. Other factors such as a positive family history of epilepsy, age at onset of febrile convulsions, or duration of the seizure were not found to be of prognostic significance.     

Alteration without change?: a commentary on the proposed policy reforms of the British National Health Service

Magnesium chloride (MgCl2) has been proposed for the treatment of seizures of different etiologies. The present study investigated the effect of MgCl2 on aldrin-induced seizures. Initially, 50 male rats received 60 mg aldrin/kg po and the effects were classified as muscular twitches, clonic convulsions or tonic-clonic convulsions. Another group of 40 rats dosed with 60 mg aldrin/kg po received 0, 4, 8, or 12 mg MgCl2/kg i.m. The percentage of tonic-clonic convulsant rats that resulted from MgCl2 treatment were 90% at 0 mg/kg, 50% at 4 mg/kg, 40% at 8 mg/kg and 20% at 12 mg MgCl2/kg. The percentage of survivors in the group receiving 12 mg MgCl2/kg was 80% while the control group had 20% survival. The clonic convulsions were not modified by MgCl2 treatment. Blood and brain concentrations of aldrin and dieldrin (metabolite of aldrin) did not differ among groups. The MgCl2 administration decreased the neuroexcitability induced by aldrin and increased survivability.     

Long-lasting effects of cholinergic stimulation of the amygdaloid complex in the rat.

Assigned 104 male Sprague-Dawley albino rats to 4 groups: (a) unoperated control, (b) cannulated control, (c) carbachol injections, and (d) eserine injections. Injection of carbachol into the amygdaloid complex caused EEG seizures and behavioral convulsions. After convulsions and abnormal EEG had disappeared, impaired acquisition of a 1-way active-avoidance response and facilitated acquisition of a 2-way shuttle-box avoidance response persisted. There was normal acquisition of an appetitive visual discrimination task, but no improvement in 1-way active-avoidance acquisition following daily handling that facilitated acquisition in controls. Eserine injections into the amygdala produced a deficit in 1-way avoidance acquisition similar to that produced by carbachol, without altering EEG or inducing convulsions. It is suggested that the behavioral changes were due to altered amygdaloid synaptic function which elevated the Ss' reactivity to noxious stimuli. (20 ref.) (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Familial infantile convulsions and paroxysmal choreoathetosis: a new neurological syndrome linked to the pericentromeric region of human chromosome 16

Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic syndromes. Paroxysmal choreoathetosis is an involuntary-movement disorder characterized by attacks that occur spontaneously or are induced by a variety of stimuli. Classification is still elusive, and the epileptic nature of this movement disorder has long been discussed and remains controversial. We have studied four families from northwestern France in which benign infantile convulsions was inherited as an autosomal dominant trait together with variably expressed paroxysmal choreoathetosis. The human genome was screened with microsatellite markers regularly spaced, and strong evidence of linkage for the disease gene was obtained in the pericentromeric region of chromosome 16, with a maximum two-point LOD score, for D16S3133, of 6.76 at a recombination fraction of 0. Critical recombinants narrowed the region of interest to a 10-cM interval around the centromere. Our study provides the first genetic evidence for a common basis of convulsive and choreoathetotic disorders and will help in the understanding and classification of paroxysmal neurological syndromes.     

Methionine sulfoximine increases acetylcholine level in the rat brain: no relation with epileptogenesis

Methionine sulfoximine induces epileptiform convulsions in rats. A possible involvement of acetylcholine in the onset of convulsions was investigated. A subconvulsive dose of methionine sulfoximine increased the brain acetylcholine concentration. After administration of a convulsive dose, atropine neither prevented the onset of the seizures nor prevented the increase in acetylcholine concentration. Physostigmine enhanced the increase in acetylcholine level but did not modify the time course nor the intensity of the convulsions. L-DOPA suppressed the seizures without inhibiting the increase in acetylcholine level. The choline content decreased after the convulsant dose. The increase in acetylcholine content is therefore not the unique cause of the seizures, which could result from the reduction of striatal inhibition due to a decrease in dopamine level induced by methionine sulfoximine.     

Corticosterone increases severity of acute withdrawal from ethanol, pentobarbital, and diazepam in mice

It has been suggested that withdrawal from several subclasses of central nervous system (CNS) depressants involves common underlying mechanisms. For example, mice genetically selected for severe ethanol withdrawal convulsions (Withdrawal Seizure Prone or WSP) have also been found to express severe withdrawal following treatment with barbiturates and benzodiazepines. Corticosteroids appear to modulate severity of withdrawal from CNS depressants. Therefore, it was hypothesized that corticosterone would enhance withdrawal convulsions following acute ethanol, pentobarbital, and diazepam in WSP mice. Corticosterone (20 mg/kg) administered following each of these drugs significantly increased severity of handling-induced convulsions during withdrawal. Corticosterone did not affect pre-withdrawal convulsion scores or handling-induced convulsions of drug-naive mice. These results suggest that withdrawal convulsions following acute ethanol, pentobarbital, and diazepam are sensitive to modulation by corticosterone and they support the hypothesis that stress may increase drug withdrawal severity.     

Conditioned effects of kindling three different sites in the hippocampal complex of the rat.

Rats received kindling stimulations to the perirhinal cortex (PRh), ventral hippocampus (VH), or dorsal hippocampus (DH) in 1 environment and an equivalent number of sham stimulations in a 2nd environment. The PRh-kindled rats displayed rapid kindling and a swift emergence of conditioned interictal defensiveness. In contrast, the VH- and DH-kindled rats displayed much slower kindling and slow or no conditioning, respectively. No effects of conditioning on the convulsions, comparable with those associated with amygdala kindling, were observed. These results establish the generality of some of the previously reported kindling-related conditioned effects, confirm the site specificity of some of these effects, and suggest that the convulsions, rather than the stimulations, function as the unconditioned stimuli for the conditioning of interictal behavior. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

NMDA receptor-mediated pilocarpine-induced seizures: characterization in freely moving rats by microdialysis

1. Pilocarpine administration has been used as an animal model for temporal lobe epilepsy since it produces several morphological and synaptic features in common with human complex partial seizures. Little is known about changes in extracellular neurotransmitter concentrations during the seizures provoked by pilocarpine, a non-selective muscarinic agonist. 2. Focally evoked pilocarpine-induced seizures in freely moving rats were provoked by intrahippocampal pilocarpine (10 mM for 40 min at a flow rate of 2 microl min(-1)) administration via a microdialysis probe. Concomitant changes in extracellular hippocampal glutamate, gamma-aminobutyric acid (GABA) and dopamine levels were monitored and simultaneous electrocorticography was performed. The animal model was characterized by intrahippocampal perfusion with the muscarinic receptor antagonist atropine (20 mM), the sodium channel blocker tetrodotoxin (1 microM) and the N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 (dizocilpine maleate, 100 microM). The effectiveness of locally (600 microM) or systemically (10 mg kg(-1) day(-1)) applied lamotrigine against the pilocarpine-induced convulsions was evaluated. 3. Pilocarpine initially decreased extracellular hippocampal glutamate and GABA levels. During the subsequent pilocarpine-induced limbic convulsions extracellular glutamate, GABA and dopamine concentrations in hippocampus were significantly increased. Atropine blocked all changes in extracellular transmitter levels during and after co-administration of pilocarpine. All pilocarpine-induced increases were completely prevented by simultaneous tetrodotoxin perfusion. Intrahippocampal administration of MK-801 and lamotrigine resulted in an elevation of hippocampal dopamine levels and protected the rats from the pilocarpine-induced seizures. Pilocarpine-induced convulsions developed in the rats which received lamotrigine perorally. 4. Pilocarpine-induced seizures are initiated via muscarinic receptors and further mediated via NMDA receptors. Sustained increases in extracellular glutamate levels after pilocarpine perfusion are related to the limbic seizures. These are arguments in favour of earlier described NMDA receptor-mediated excitotoxicity. Hippocampal dopamine release may be functionally important in epileptogenesis and may participate in the anticonvulsant effects of MK-801 and lamotrigine. The pilocarpine-stimulated hippocampal GABA, glutamate and dopamine levels reflect neuronal vesicular release.     

Development of a novel rat mutant with spontaneous limbic-like seizures

A new epileptic rat mutant with spontaneous seizures was developed by successive mating and selection from an inherited cataract rat. The procedures for developing the mutant and the symptomatology, electroencephalographic correlates, and neuropathology of the mutant are reported. It is possible that this rat stain will provide a useful animal model for human temporal lobe epilepsy. The seizures of the rat usually begin with face and head myoclonus, followed by rearing, and generalized clonic and tonic convulsions, all of which are symptomatologically the same as limbic seizures. Electrographic recording during generalized convulsive seizures demonstrated that sustained spike discharges emerged at the hippocampus and then propagated to the neocortex. Seizures occurred spontaneously without any artificial stimuli. Furthermore, external stimuli such as auditory, flashing light, or vestibular stimulations could not elicit epileptic attacks. Almost all of the male animals had generalized convulsions, mostly from 5 months after birth, and the frequency of the seizures increased with aging. Generalized convulsions developed in approximately 20% of the female rats. Microdysgenesis, such as abnormal neuronal clustering, neuronal disarrangement, or interruption of pyramidal neurons in the hippocampal formation, was found in the young rats that had not yet had generalized seizures. This microdysgenesis, which is though to be genetically programmed, was very interesting from the aspect of the relationship between structural abnormalities and epileptogenesis in this mutant. In addition to microdysgenesis, there was sprouting of mossy fibers into the inner molecular layer of the dentate gyrus in those adult rats that had repeated generalized convulsions. An increase of glial-fibrillary-acidic-protein-positive astrocytes with thickened and numerous processes, ie, astrogliosis, was also found in the cerebral cortex, amygdala region, and hippocampus of these adult animals. Judging from the characteristics of the symptomatology, electroencephalographic correlates, and neuropathology, this epileptic mutant can be expected to be a useful animal model for studying human temporal lobe epilepsy.     

Effects of phenobarbital and diazepam on imipramine-induced changes in blood pressure, heart rate and rectal temperature of rats

To investigate the safety of anticonvulsants in doses found equipotent in suppressing imipramine induced convulsions, the effects of diazepam (1.8 mg/kg) or phenobarbital (40 mg/kg) following a toxic dose of imipramine (50 mg/kg) on heart rate, blood pressure and body temperature were examined in male Wistar rats. Administration of imipramine alone resulted in significant decreases in blood pressure, heart rate and rectal temperature. Phenobarbital or diazepam alone failed to significantly affect any of these parameters apart from a slight reduction in rectal temperature seen with phenobarbital. Diazepam given after imipramine antagonized the imipramine-induced decrease in heart rate but increased the hypotensive and hypothermic effects. Phenobarbital failed to significantly affect the imipramine-induced changes in any of the physiological parameters studied. The present data suggests that phenobarbital may be preferable to diazepam in treatment of imipramine-induced convulsions.     

First-order projections activated by stimulation of hypothalamic sites eliciting attack and flight in rats.

–2–4C-deoxyglucose autoradiographs of attack rats were compared densitometrically with those of control rats whose electrodes were located nearby and elicited nonaggressive behaviors like those that accompanied the attack. Most closely associated with attack was the path from the ventromedial hypothalamus through the ventral supraoptic commissural pathway to the peripeduncular area, subparafascicular nucleus, zone incerta, and cuneiform area. Moderately correlated with attack were 4 visual areas: the dorsal and ventral lateral geniculate nuclei, pretectal area, and superior colliculus. Activity in the periaqueductal gray was unrelated to attack ipsilaterally and only weakly related contralaterally. In an orthogonal analysis, upward-oriented flight thresholds were significantly correlated with medial activation extending anteriorly to the lateral septal nucleus, dorsally to the thalamic paraventricular-parataenial region, and posteriorly to the periaqueductal gray. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Tritiated 18-hydroxydeoxycorticosterone: binding in renal, cardiac and hepatic cytoplasm, and in plasma from adrenalectomized rats

A seven months old infant suffered from convulsions due to leucine-sensitive hypoglycaemia. The convulsions could not be stopped by a diet lacking in leucine, but ceased after additional application of diazoxide; hypoglycaemia was no longer observed the mental development of the child is hoped to be normal.     

Pancreatic cancer cells selectively stimulate islet beta cells to secrete amylin

The goal of the studies described was to evaluate the role of NMDA receptor-mediated glutamate excitotoxicity in the pathogenesis of selective neuronal loss due to thiamine deficiency. Administration of the central thiamine antagonist pyrithiamine to adult male rats resulted in a sequence of neurological symptoms including ataxia and loss of righting reflex followed by convulsions. Prior to the onset of convulsions, neuropathologic evaluation revealed significant neuronal loss in the ventral posterior medial thalamic nucleus. However, in vivo cerebral microdialysis at preconvulsive stages did not demonstrate significant increases of extracellular glutamate in this region and pretreatment with the NMDA receptor antagonist MK801 (1 mg/ kg/12 h, i.p.) did not afford significant neuroprotection. Following the onset of convulsions, microdialysate glutamate concentrations were increased fivefold (P > 0.05) and MK801 treatment resulted in significant attenuation of neuronal loss in some thalamic nuclei. A comparable degree of neuroprotection was afforded by pretreatment with an anticonvulsant dose of diazepam (10 mg/kg/12 h, i.p.) a compound whose action is not NMDA receptor mediated. These findings suggest that NMDA receptor-mediated excitotoxicity is not responsible for early selective neuronal loss in this model of thiamine deficiency encephalopathy and that the neuroprotective effect of MK801 at later stages are at least in part a consequence of its anticonvulsant properties.     

Brain damage by extracts of parasitised annual ryegrass (Lolium rigidum) in nursling rats

Extracts of annual ryegrass (Lolium rigidum) infected with Anguina sp. and Corynebacterium sp., and associated with an outbreak of annual ryegrass toxicity in sheep, were administered to 2-week-old rats by a single intraperitoneal injection. Rats that received a lethal dose of toxin developed neurological signs including incoordination and convulsions from the second day and most died between 2 and 7 days after injection. Histologically, the brains showed widespread lesions of focal necrosis consistent with anoxia. Peripheral circulation rate was greatly reduced after 3 days and gangrene of the tail and hind legs developed in some rats. Evidence of restricted blood flow was also seen in kidneys, lungs and brain. It was concluded that the toxin contains a long-acting vasoconstrictor.     

The role of catecholamines in cocaine toxicity: a model for cocaine "sudden death"

Sudden death associated with cocaine abuse is preceded by a state of agitated delirium. We postulated that release of catecholamines associated with this stress enhanced toxicity from cocaine. Thus we investigated the effect of catecholamine infusion [(epinephrine (7.25 ugml-1), norepinephrine (4.4 ugml-1) and dopamine (8.0 ugml-1), infused at 6 ml h-1] on the toxicity from concomitant infusion of cocaine (1 mg-kg-1 min-1). Two groups of rats were studied in order to isolate distinct toxicity endpoints: convulsions and respiratory arrest in conscious, and, circulatory arrest in anesthetized and ventilated rats. Catecholamines were administered at either full or 1/2 strength to establish a dose response effect on cocaine toxicity. Catecholamine infusion in a dose dependent fashion provoked earlier convulsions and respiratory arrest in conscious rats and circulatory arrest in anesthetized and ventilated rats. Despite lower cocaine cumulative dose administration, rats receiving catecholamines had similar plasma cocaine concentrations at the onset of convulsions and respiratory arrest compared to those with cocaine infusion alone. The data suggest that catecholamines enhance the convulsive, respiratory and circulatory toxicity of cocaine by a pharmacokinetic interaction.     

Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat.

Two experiments with 38 rats examined the neurotoxic effects of domoic acid. In Exp 1, iv injection of 0.5–2.0 mg/kg or intraventricular (ivc) injection of 0.04–0.08 μg of domoic acid caused seizures in the hippocampus, tonic-clonic convulsions, and death within a few days. Convulsions and ensuing death were prevented by diazepam. Ss pretreated with intraperitoneal/ly (ip) diazepam (5 mg/kg) tolerated an ivc dose of domoic acid of 0.4 μg, but showed a loss of pyramidal neurons mainly in the CA3, the CA4, and a part of the CA1 areas of the dorsal hippocampus. In Exp 2, learning of a radial maze task was severely impaired in naive Ss after ivc injection of domoic acid (and diazepam, ip). In Ss previously trained on the maze task, domoic acid interfered with relearning of the same task. (French abstract) (PsycINFO Database Record (c) 2010 APA, all rights reserved)