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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An animal model of focal herpes simplex encephalitis was used to study several strains of type-1 herpes simplex virus. Rabbits were inoculated in the olfactory bulb by a standardized technique. Virus strains resulting in mortality of greater than 70% produced seizures of 3 types, and all animals that seized became moribund or died. In contrast, a virus strain resulting in a 20% mortality produced no seizures. Administration of 60 mg phenobarbital intramuscularly daily reduced mortality significantly in animals given the epileptogenic viruses. Cultures from temporal and frontal lobes showed viral growth more frequently than did cultures of other brain areas. Microscopic examination of routine and immunoperoxidase-stained brain sections confirmed the focal nature of the infection. Clinical syndromes such as seizures arising from viral brain disease may influence mortality in animal model systems.
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PMID:Neurovirulence in an experimental focal herpes encephalitis: relationship to observed seizures. 283 94

The prepiriform cortex (PPCx) shows high sensitivity to the epileptogenic action of chemo-convulsants and to the protective action of the NMDA receptor antagonist, 2-amino-7-phosphono-heptanoate (APH) against pilocarpine-induced (motor) limbic seizures in rats. In this study the interaction between agonists acting selectively on the three main excitatory amino acid receptor subtypes in the PPCx and the muscarinic agonist, pilocarpine, within the PPCx have been investigated. Kainate (KA) or quisqualate (QUIS) injected focally into the PPCx (100 pmoles or 5 nmoles per side respectively) induced motor limbic seizures when administered after a subconvulsant dose of pilocarpine (250 mg/kg, i.p.). KA, 100 pmoles injected into the same site in olfactory-bulboectomized rats (bulbectomy results in protection against pilocarpine-induced seizures) also facilitated seizures. However, activation of the NMDA receptor in the PPCx by focal injection of NMDA (250 fmoles-10 nmoles) failed to produce seizures after a subconvulsant dose of pilocarpine. Moreover NMDA in the same range of doses injected into the PPCx protected rats against the seizures induced by a fully convulsant dose of pilocarpine.
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PMID:The involvement of excitatory amino acid receptors within the prepiriform cortex in pilocarpine-induced limbic seizures in rats. 285 76

The use of a multidisciplinary approach--laboratory and clinical pharmacology and experimental and human neurochemistry--has demonstrated that GABA neurons and receptors play a variety of functional roles in the mammalian brain. The present synopsis has been limited to some of the newer aspects of GABA neuron function. Thus there is strong evidence that GABA neurons are involved in the control of cerebral excitability (cf. tables I, II) and in the genesis of at least some seizures states, including certain types of human epilepsy (table III). Furthermore GABA receptor activation can be used to control seizures of diverse etiology and at least one GABA agonist, progabide, is effective in human epilepsy. There is a foundation for the belief that GABA neurons function in the control of affect and emotion. The most convincing evidence is from laboratory and clinical pharmacology studies in depression and models for the development of new antidepressant drugs. GABA agonists act as antidepressants not only in animal models such as learned helplessness, olfactory bulbectomy and the sleep-cycle but also demonstrate an antidepressant action in man. Additionally, the recent studies showing that chronic treatment by antidepressants, induce an increase in 3H-GABA "B" binding strongly support a GABAergic contribution in the mechanism of antidepressant drugs (cf. table IV). There is also some evidence for the hypothesis that GABA neurons and receptors participate in the biology of anxiety, or at least the mechanism of action of anxiolytics. This is based mainly on the known molecular pharmacology of the benzodiazepine receptor and the evidence in animal models for anxiety (table V). However in clinical trials the GABA agonist progabide is only a weak anxiolytic. A major function of GABA neurons and receptors is the regulation of the nigro-striatal dopamine pathway (table VI) and the expression of dopamine receptor mediated events (table VII). This modulation probably occurs via at least 3 mechanisms: a tonic inhibition of dopamine neuron activity regulating dopamine synthesis, turnover and release; a long term modulation controlling striatal dopamine receptor numbers, modification of the expression of dopaminergic transmission distal to the dopaminergic synapse.
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PMID:[Implications of GABAergic synapses in neuropsychiatry]. 286 52

The role of central noradrenergic neurons in kindled seizures was assessed by comparison of alpha 2- and beta-adrenoceptor binding in the cerebral cortex from kindled and control rats. To minimize handling, which may modify kindling-induced changes in binding, the kindling protocol involved stimulation of the amygdala every hour for a maximum of 26 h. Twenty-four hours after kindling, down-regulation of beta-adrenoceptors was found in both olfactory cortex and the remaining neocortex, whereas alpha 2 down-regulation was confined to the olfactory cortex. At 21 days after kindling, the only change found was a down-regulation of beta-adrenoceptors in the neocortex. The results support the view that functional changes in central noradrenergic transmission are associated with the reduction in seizure threshold induced by kindling.
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PMID:Down-regulation of alpha 2- and beta-adrenoceptor binding sites in rat cortex caused by amygdalar kindling. 299 10

Seizures produced by pilocarpine given i.p. to rats provide an animal model for studying the initiation, spread and generalisation of convulsive activity within the forebrain. Pilocarpine, 380 mg/kg, produces a sequence of behavioural and electroencephalographic alterations indicative of motor limbic seizures and status epilepticus, which is followed by widespread damage to the limbic forebrain resembling that occurring subsequent to prolonged intractable seizures. Microinjections of a selective antagonist at the N-methyl-D-aspartate receptor, (+/-)-2-amino-7-phosphonoheptanoate, into the substantia nigra pars reticulata, bilaterally, protects against the behavioural, electrographic and morphological features of seizures produced by pilocarpine, 380 mg/kg, with an ED50 of 0.0007 mumol (0.0004-0.0011). Microinjections of (+/-)-2-amino-7-phosphonoheptanoate, 0.005 or 0.01 mumol, into the substantia nigra pars compacta or into the dorsal part of mid-anterior striatum do not modify the electrographic and morphological sequelae of pilocarpine, 380 mg/kg. In rats pretreated with microinjections of N-methyl-D-aspartate into the substantia nigra pars reticulata, a non-convulsive dose of pilocarpine, 100 mg/kg, results in recurrent motor limbic seizures and status epilepticus. The ED50 of N-methyl-D-aspartate for the generation of seizures after pilocarpine, 100 mg/kg, is 0.0014 mumol (0.001-0.0019). Electrographic monitoring shows a pattern and sequence of evolution of convulsant activity within the hippocampus and cortex similar to that produced with pilocarpine, 380 mg/kg, alone. Morphological examination of brains from rats treated with N-methyl-D-aspartate in the substantia nigra pars reticulata and subsequently given pilocarpine, 100 mg/kg, which underwent status epilepticus, reveals widespread damage to the amygdala, thalamus, olfactory cortex, substantia nigra, neocortex, and hippocampus. Microinjections of N-methyl-D-aspartate, 0.002 mumol, into either the substantia nigra pars compacta or dorsal striatum, bilaterally, do not augment seizures produced by pilocarpine, 100 mg/kg. The results indicate that the threshold for pilocarpine-induced seizures in rats is modulated by excitatory amino acid neurotransmission within the substantia nigra pars reticulata.
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PMID:Excitatory neurotransmission within substantia nigra pars reticulata regulates threshold for seizures produced by pilocarpine in rats: effects of intranigral 2-amino-7-phosphonoheptanoate and N-methyl-D-aspartate. 301

The olfactory bulb (OB), anterior olfactory nucleus (AON) and prepyriform cortex (PC) maintain 3 kinds of feedback among their populations of excitatory and inhibitory neurons: negative feedback, mutual excitation, and mutual inhibition. At normal levels of synaptic input these are balanced and give rise to chaotic and near-sinusoidal oscillatory EEG activity. Under intense repetitive electrical stimulation of the lateral olfactory tract (LOT), there is failure of the afferent excitatory terminals, perhaps due to transmitter depletion. In this circumstance there is deficient excitatory input under the condition of a high level of sustained activity among mutually inhibitory neurons. An instability develops in which some inhibitory neurons become more disinhibited (excited) and others more inhibited (less active) to the point of a paroxysmal discharge that is manifested in a massive compound IPSP of the excitatory neurons. The paroxysm terminates abruptly, but by mechanisms still unclear repeats at a rate of about 3/s for 10-70 s. It is accompanied by simultaneous ipsilateral twitching of the eyelids and muzzle, salivation, tearing, arrest, and lack of responding to sensory stimuli but without loss of posture, resembling absence in humans. It does not result from runaway mutual excitation, and it rarely culminates in full-blown convulsions. Similar spikes usually also occur in the OB and AON; the sequences of spikes appear to entrain. These normal and seizure EEGs are simulated with a network of non-linear differential equations, that is designed in conformance with the anatomy and physiology of the olfactory system. The seizure appears as an emergent property of the OB, AON and PC interactive system, that is due to an induced asymmetry in the feedback network that controls normal background activity.
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PMID:Petit mal seizure spikes in olfactory bulb and cortex caused by runaway inhibition after exhaustion of excitation. 309 98

Increasing doses of naloxone hydrochloride (100-1000 nmol) were micro-injected unilaterally into the rat amygdala and the behavioral, neuropathological and electrographic responses were studied. Microinjections of low doses of naloxone (100-250 nmol) produced staring, gustatory automatisms and wet shakes whereas higher doses additionally resulted in motor limbic seizures and status epilepticus. The electroencephalogram showed a sequence of alterations characterised by high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and postictal depression which first appeared in the amygdala and rapidly spread to hippocampal and cortical areas. The neuropathological analysis of frontal forebrain sections by means of light microscopy revealed seizure-related brain damage in amygdala, olfactory cortex, thalamus, hippocampal formation, substantia nigra and neocortex. Diazepam, 10 mg/kg i.p., when given prior to the microinjection of naloxone into the amygdala, abolished the epileptogenic and neurotoxic effects of the drug. The results suggest that naloxone, when microinjected into rat amygdala elicits electrographic and motor limbic seizures followed by seizure-related brain damage.
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PMID:Convulsant action of naloxone in the rat amygdala. 312 74

Microinjection of morphine hydrochloride into the substantia nigra pars reticulata, bilaterally, converts non-convulsant dose of pilocarpine hydrochloride, 100 mg/kg, into a convulsant one. The ED50 of morphine for the generation of seizures after pilocarpine, 100 mg/kg, is 3.8 nmol (2.5-5.8). Electrographic and behavioral monitoring both show a pattern of convulsant activity similar to those produced by pilocarpine in doses exceeding 350 mg/kg. Morphological analysis of frontal forebrain sections reveals epilepsy-related damage to the hippocampus, thalamus, olfactory cortex, substantia nigra, neocortex and amygdala. The proconvulsant action of morphine in the substantia nigra is reversed by co-administration of naloxone hydrochloride. The results show that the threshold for limbic seizures may be modulated by opiates in the substantia nigra.
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PMID:The threshold for limbic seizures in rats is decreased by intranigral morphine. 312 75

The basal ganglia are involved in the organization of movement and function in the initiation and expression of generalized and limbic seizures. Dopamine is the principal neurotransmitter of the mesencephalic efferent pathways terminating in the mammalian striatum. No function has been ascribed to mesostriatal dopamine in the control of seizure spread in the brain. This work presents evidence that bilateral application of picomole amounts of apomorphine (a dopamine agonist) into the striatum confers protection against seizures produced by pilocarpine (a cholinergic agonist) in rats. The anticonvulsant effect of apomorphine is topographically confined to the caudate-putamen, nucleus accumbens, and olfactory tubercle. Bilateral application of nanomolar amounts of haloperidol (a dopamine antagonist) into the caudate-putamen or systemic application of haloperidol both lower the threshold for pilocarpine-induced seizures. Local application of an excitatory amino acid N-methyl-D-aspartate, into the substantia nigra pars compacta, ventral tegmental area, or retrorubral area, sites of origin of mesostriatal dopaminergic pathways, protects rats against seizures produced by pilocarpine. These results suggest that dopaminergic transmission in the striatum may be operative in complex neuronal networks modulating the seizure threshold.
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PMID:Dopamine-sensitive anticonvulsant site in the rat striatum. 318 11

Morphine hydrochloride (25-200 nmol), [D-Ala2, D-Leu5]enkephalin (10-200 nmol) and naloxone hydrochloride (100-1000 nmol) were injected unilaterally into the rat amygdala and the following electrographic, behavioural and neuropathological responses were studied. Microinjections of low doses of morphine (25-50 nmol) resulted in behavioural alterations characterized by staring, gustatory automatisms and wet shakes, whereas higher doses additionally produced motor limbic seizures and status epilepticus. The first changes in the electroencephalogram appeared in the amygdala immediately after the administration of morphine and rapidly spread to hippocampal and cortical areas. Electrographic alterations consisted of high voltage fast activity, spiking, bursts of polyspiking, electrographic seizures and periods of postictal depression. Neuropathological analysis of frontal forebrain sections by means of light microscopy revealed widespread, seizure-related damage confined to amygdala, olfactory cortex, thalamus, hippocampal formation, neocortex and substantia nigra. Pretreatment of animals with naloxone, 2-20 mg/kg s.c., as well as simultaneous microinjection of the non-convulsant dose of naloxone, 100 nmol, with morphine, 100 nmol, into the amygdala failed to block the development of convulsant activity and seizure-related brain damage produced by the opiate. In contrast, diazepam, 10 mg/kg i.p., when administered prior to the microinjection of morphine into the amygdala, abolished the epileptogenic effects of the drug. [D-Ala2, D-Leu5]Enkephalin, 10-200 nmol, elicited electrographic and behavioural responses similar to those seen after low doses of morphine, when administered into the amygdala. High voltage fast activity, single spikes, bursts of polyspiking, electrographic seizures and periods of postictal depression were seen in the electroencephalogram, but no behavioural signs of motor limbic seizures could be detected. The only behavioural correlates of epileptiform electrographic activity were wet shakes, myoclonic head twiches and gustatory automatisms. The examination of frontal forebrain sections from rats receiving [D-Ala2, D-Leu5]enkephalin revealed no morphological changes. Pretreatment of rats with either naloxone, 2 mg/kg, or diazepam, 10 mg/kg, blocked the development of behavioural and electrographic sequelae of the peptide. Naloxone, 100-1000 nmol, when microinjected into the amygdala, produced electrographic, behavioural and morphological alterations resembling those seen after high doses of morphine.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Convulsant action of morphine, [D-Ala2, D-Leu5]-enkephalin and naloxone in the rat amygdala: electroencephalographic, morphological and behavioural sequelae. 329 87


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