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Query: UMLS:C0038220 (status epilepticus)
 7,272 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe a novel model of status epilepticus produced by the focal application of bicuculline methiodide into the deep prepiriform cortex of rats pretreated with lithium chloride. Three out of eight rats pretreated with one dose of lithium (3 mmol/kg) 24 h prior to induction of seizures by focal bicuculline, and eight out of 12 rats pretreated with two doses of lithium (at 24 and 48 h) prior to seizure induction, exhibited continual uninterrupted convulsive seizure activity (status epilepticus) lasting between 10 min and > 2 h. This status epilepticus which was manifest both behaviorally and electroencephalographically, was sensitive to reversal by diazepam (5 mg/kg i.p.) given as long as 2 h after the onset of sustained status epilepticus. Pilocarpine (25 mg/kg) pretreatment also predisposed to status epilepticus in response to the focal application of bicuculline, but diazepam (5 or 10 mg/kg i.p.) was ineffective in suppressing the status epilepticus in the presence of pilocarpine.
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PMID:A rodent model of focally evoked self-sustaining status epilepticus. 145 87

Pilocarpine-induced status epilepticus leads to widespread limbic forebrain damage in rats and provides a model for studying intractable epilepsy. Noradrenergic neurons in suspension, prepared from the locus coeruleus region of donors on the 13th or 14th gestational day, were microinjected bilaterally into the hippocampus (8 rats) and into the cerebellum (4 rats) or the olfactory bulb (4 rats) of epileptic rats. Three microliters of suspension was deposited at the rate of 1 microliter/min. Control animals were not submitted to surgery (4 rats). After six weeks a marked reduction of suppression of spontaneous seizures was observed in intrahippocampally grafted rats. From these preliminary results we suggest that grafts can be used to suppress spontaneous recurrent epileptic seizures.
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PMID:Some evidence that intrahippocampal grafting of noradrenergic neurons suppresses spontaneous seizures in epileptic rats. 213 60

High-dose treatment with pilocarpine hydrochloride, a cholinergic muscarinic agonist, induces seizures in rodents following systemic or intracerebral administration. Pilocarpine seizures are characterized by a sequential development of behavioral patterns and electrographic activity. Hypoactivity, tremor, scratching, head bobbing, and myoclonic movements of the limbs progress to recurrent myoclonic convulsions with rearing, salivation, and falling, and status epilepticus. The sustained convulsions induced by pilocarpine are followed by widespread damage to the forebrain. The amygdala, thalamus, olfactory cortex, hippocampus, neocortex, and substantia nigra are the most sensitive regions to epilepsy-related damage following convulsions produced by pilocarpine. Spontaneous seizures are observed in the long-term period following the administration of convulsant doses of pilocarpine. Developmental studies show age-dependent differences in the response of rats to pilocarpine. Seizures are first noted in 7-12 day-old rats, and the adult pattern of behavioral and electroencephalographic sequelae of pilocarpine is seen in 15-21-day-old rats. During the third week of life the rats show an increased susceptibility to the convulsant action of pilocarpine relative to older and younger animals. The developmental progress of the convulsive response to pilocarpine does not correlate with evolution of the brain damage. The adult pattern of the damage is seen after a delay of 1-2 weeks in comparison with the evolution of seizures and status epilepticus. The susceptibility to seizures induced by pilocarpine increases in rats aged over 4 months. The basal ganglia curtail the generation and spread of seizures induced by pilocarpine. The caudate putamen, the substantia nigra, and the entopeduncular nucleus govern the propagation of pilocarpine-induced seizures. The antiepileptic drugs diazepam, clonazepam, phenobarbital, valproate, and trimethadione protect against pilocarpine-induced convulsions, while diphenylhydantoin and carbamazepine are ineffective. Ethosuximide and acetazolamide increase the susceptibility to convulsant action of pilocarpine. Lithium, morphine, and aminophylline also increase the susceptibility of rats to pilocarpine seizures. The pilocarpine seizure model may be of value in designing new therapeutic approaches to epilepsy.
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PMID:Review: cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine: a novel experimental model of intractable epilepsy. 264 33

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

Seizures produced by systemic administration of pilocarpine hydrochloride, a cholinergic muscarinic agonist, in rodents are proposed as a useful animal model of epilepsy. Pilocarpine-induced seizures in rats and mice are characterized by sequential development of behavioral and electrographic signs, which are followed by widespread damage to the forebrain (hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra). Spontaneous seizures may be observed in the long-term period following the administration of convulsant doses of pilocarpine. In experiments designed to examine neuronal networks engaged in the generation and spread of pilocarpine-induced convulsions, a marked role for the basal ganglia is demonstrated. The caudate-putamen, the substantia nigra and the entopeduncular nucleus were found to govern the propagation of seizures produced by pilocarpine. The antiepileptic potential of drugs (diazepam, clonazepam, phenobarbital, valproic acid and trimethadione) against pilocarpine-induced convulsions correlates with their depressant action on the spontaneous activity of non-dopaminergic cells in the substantia nigra. Developmental studies show age-dependent differences in the convulsant response of rats to pilocarpine and status epilepticus are first noted in 2-3 week-old rats, but there is no clear-cut correlation between seizures and evolution of brain damage at this age. The adult pattern of the damage to forebrain is seen after a delay of 1-2 weeks relative to the development of seizures and status epilepticus. The research on the pilocarpine model of convulsions and other cholinergically mediated seizure syndromes may be of value for designing new therapeutic approaches to epilepsy in.
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PMID:The seizures induced by pilocarpine: behavioral, electroencephalographic and neuropathological studies in rodents. 333 12

Behavioral, electroencephalographic and morphological changes induced by systemic administration of pilocarpine hydrochloride were studied in 3-90-day-old rats. Pilocarpine, 100, 200 and 380 mg/kg, presented a characteristic array of behavioral patterns in developing rats. Hyper- or hypoactivity, tremor, loss of postural control, scratching, head bobbing and myoclonic movements of the limbs dominated the behavior in 3-9-day-old rats. No overt motor seizures were observed in this age group. More intense behavioral signs evolving in some animals to limbic seizures and status epilepticus occurred when pilocarpine was administered in 12-day-old-rats. The electrographic activity in these animals progressed from low voltage spiking registered concurrently in the hippocampus and cortex during the first week of life into localized epileptic activity in the hippocampus, which spread to cortical recordings during the second week of life. No morphological alterations were detected in the brains of 3-12-day-old rats subjected to the action of pilocarpine, 100-380 mg/kg. The adult pattern of behavioral and electroencephalographic sequelae after pilocarpine was encountered in 15-21-day-old rats. Akinesia, tremor and head bobbing progressed in 15-21-day-old rats given pilocarpine, 100-380 mg/kg, to motor limbic seizures and status epilepticus. The lethal toxicity of pilocarpine reached 50% during the third week of life. This increased susceptibility to the convulsant action of pilocarpine was characterized by a shortened latency for behavioral and electrographic signs, and an increased severity of seizures relative to older and younger rats. In 15-21-day-old rats subjected to pilocarpine-induced convulsions high voltage fast activity superposed over hippocampal theta-rhythm, progressed into high voltage spiking and spread to cortical records. The electrographic activity became well synchronized and then developed into seizures and status epilepticus. Morphological analysis of frontal forebrain sections in 15-21-day-old rats which underwent status epilepticus after pilocarpine revealed no damage or an attenuated pattern of damage. In 15-21-day-old rats which presented epilepsy-related brain damage, morphological breakdown was seen in the hippocampus, amygdala, olfactory cortex, neocortex and certain thalamic nuclei. No damage was detected in the substantia nigra and lateral thalamic nucleus. An adult pattern of the damage to the brain, in terms of extent and topography, was present in 4-5-week-old rats.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The susceptibility of rats to pilocarpine-induced seizures is age-dependent. 344 Feb 12

Pilocarpine, given intraperitoneally to rats, reproduces the neuropathological sequelae of temporal lobe epilepsy and provides a relevant animal model for studying mechanisms of buildup of convulsive activity and pathways operative in the generalization and propagation of seizures within the forebrain. In the present study, the effects of manipulating the activity of the gamma-aminobutyric acid (GABA)-mediated synaptic inhibition within the substantia nigra on seizures produced by pilocarpine in rats, were investigated. In animals pretreated with microinjections of isoniazid, 150 micrograms, an inhibitor of activity of the GABA-synthesizing enzyme, L-glutamic acid decarboxylase, into the substantia nigra pars reticulata (SNR), bilaterally, non-convulsant doses of pilocarpine, 100 and 200 mg/kg, resulted in severe motor limbic seizures and status epilepticus. Electroencephalographic and behavioral monitoring revealed a profound reduction of the threshold for pilocarpine-induced convulsions. Morphological analysis of frontal forebrain sections with light microscopy revealed seizure-related damage to the hippocampal formation, thalamus, amygdala, olfactory cortex, substantia nigra and neocortex, which is typically observed with pilocarpine in doses exceeding 350 mg/kg. Bilateral intrastriatal injections of isoniazid did not augment seizures produced by pilocarpine, 200 mg/kg. Application of an irreversible inhibitor of GABA transaminase, gamma-vinyl-GABA (D,L-4-amino-hex-5-enoic acid), 5 micrograms, into the SNR, bilaterally, suppressed the appearance of electrographic and behavioral seizures produced by pilocarpine, 380 mg/kg. This treatment was also sufficient to protect animals from the occurrence of brain damage. Microinjections of gamma-vinyl-GABA, 5 micrograms, into the dorsal striatum, bilaterally, failed to prevent the development of convulsions produced by pilocarpine, 380 mg/kg. The results demonstrate that the threshold for pilocarpine-induced seizures in rats is subjected to the regulation of the GABA-mediated synaptic inhibition within the substantia nigra.
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PMID:Susceptibility to seizures produced by pilocarpine in rats after microinjection of isoniazid or gamma-vinyl-GABA into the substantia nigra. 370 28

Increasing doses of pilocarpine, 100-400 mg/kg, were given intraperitoneally to mice and the resulting behavioral, electroencephalographic and neuropathological alterations were studied. No behavioral phenomena were observed in mice treated with the lowest dose of pilocarpine. Occasional tremor and myoclonus of hindlimbs were found in animals which received pilocarpine in a dose of 200 mg/kg. At doses of 300, 325 and 350 mg/kg, pilocarpine produced a sequence of behavioral alterations including staring spells, limbic gustatory automatisms and motor limbic seizures that developed over 15-30 min and built up progressively into a limbic status epilepticus lasting for several hours. The highest dose of pilocarpine, 400 mg/kg, was generally lethal to mice. Pilocarpine produced both interictal and ictal epileptiform activity in the electroencephalogram (EEG). The earliest EEG alterations appeared in the hippocampus and then spread to cortical areas. EEG seizures started 10-15 min after injection of large doses of pilocarpine, 300-350 mg/kg. Ictal periods lasted for 1-2 min, recurred every 5-10 min and were followed by periods of depression of the EEG activity. By 30-45 min paroxysmal activity resulted in a status epilepticus. Examination of frontal forebrain sections with light microscopy revealed a widespread damage to several brain regions including the hippocampus, amygdala, thalamus, olfactory cortex, neocortex and substantia nigra. Scopolamine, 10 mg/kg, and diazepam, 10 mg/kg, prevented the development of convulsive activity and brain damage produced by pilocarpine. The results emphasize that excessive and sustained stimulation of cholinergic receptors can lead to seizures and seizure-related brain damage in mice. It is proposed that systemic pilocarpine in mice provides a useful animal model for studying mechanisms of and therapeutic approaches to temporal lobe epilepsy.
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PMID:Seizures produced by pilocarpine in mice: a behavioral, electroencephalographic and morphological analysis. 649 17

Neurotrophins such as NT-3 are subject to complex regulation during epileptic seizures. Pilocarpine at a dose of 250 mg/kg induced either limbic seizures (LS) or limbic motor status epilepticus (LMSE) in adult rats. In situ hybridization signals for NT-3 mRNA declined moderately after LS and were nearly lost in LMSE at 3-4 h. Loss of NT-3 mRNA expression does not correlate with cell death and may reflect a functional down-regulation in certain hippocampal neurons.
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PMID:Decrease of neurotrophin-3 mRNA in adult rat hippocampus after pilocarpine seizures. 749 9

We used the pilocarpine model of chronic spontaneous recurrent seizures to evaluate the time course of supragranular dentate sprouting and to assess the relation between several changes that occur in epileptic tissue with different behavioral manifestations of this experimental model of temporal lobe epilepsy. Pilocarpine-induced status epilepticus (SE) invariably led to cell loss in the hilus of the dentate gyrus (DG) and to spontaneous recurrent seizures. Cell loss was often also noted in the DG and in hippocampal subfields CA1 and CA3. The seizures began to appear at a mean of 15 days after SE induction (silent period), recurred at variable frequencies for each animal, and lasted for as long as the animals were allowed to survive (325 days). The granule cell layer of the DG was dispersed in epileptic animals, and neo-Timm stains showed supra- and intragranular mossy fiber sprouting. Supragranular mossy fiber sprouting and dentate granule cell dispersion began to appear early after SE (as early as 4 and 9 days, respectively) and reached a plateau by 100 days. Animals with a greater degree of cell loss in hippocampal field CA3 showed later onset of chronic epilepsy (r = 0.83, p < 0.0005), suggesting that CA3 represents one of the routes for seizure spread. These results demonstrate that the pilocarpine model of chronic seizures replicates several of the features of human temporal lobe epilepsy (hippocampal cell loss, supra- and intragranular mossy fiber sprouting, dentate granule cell dispersion, spontaneous recurrent seizures) and that it may be a useful model for studying this human condition. The results also suggest that even though a certain amount of cell loss in specific areas may be essential for chronic seizures to occur, excessive cell loss may hinder epileptogenesis.
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PMID:Circuit mechanisms of seizures in the pilocarpine model of chronic epilepsy: cell loss and mossy fiber sprouting. 769 49


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