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

Intra-amygdaloid unilateral application of low doses of kainic acid rapidly elicits, in both chronic and acute conditions, secondarily generalized convulsive seizures which often culminate in fatal true status epilepticus unless appropriate anti-epileptic drugs are provided. Spontaneous recurrent seizures are observed for several hours starting approximately 10 min. after the application of kainic acid. In addition to the primary degeneration in the amygdaloid complex, a secondary cell loss is seen in CA3 area of the dorsal hippocampus. It is suggested that this procedure may constitute a particularly suitable model for the study of true focalized status epilepticus.
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PMID:[Epileptogenic action of intra-amygdaloid injection of kainic acid]. 10 52

In rabbits epileptiform seizures were induced by systemic application of methoxypyridoxine, an antimetabolite of vitamin B6. The regional distribution of GABA was measured in 11 brain structures, before the onset of the seizure and during the generalized convulsions. In brain regions with a high GABA level the GABA content drops already preictally, in contrast to the GABA poor structures where no preictal decrease takes place. From this it is concluded that there exist two GABA pools, a functional one containing the GABA for chemical transmission, which is exhausted already preictally giving rise to the seizure discharges, and a metabolic one, which is utilized as an additional energy-source during the convulsions. Due to the decrease of the hippocampal GABA the endings of the dentate gyrus granule cells, the giant boutons contacting the apical dendrites of the pyramidal cells of CA3 and CA4, can discharge unrestrained. An ultrastructural correlate of the increased excitation is demonstrated. The dense-core vesicles of the giant boutons fuse in an omega-shaped form with the presynaptic membrane of the spines. This fusion-phenomenon is observed in ultrathin sections as well as in freeze-fractured replicas of this region.
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PMID:Antivitamin B6 induced ultrastructural changes in the hippocampus of the convulsant rabbit and its biochemical correlates. 99 35

Immunohistological and in situ hybridization techniques were used to study the influence of kainic acid-induced seizures and of pentylenetetrazol kindling on neurokinin B immunoreactivity and neurokinin B mRNA in the rat hippocampus. Pronounced increases in neurokinin B immunoreactivity were observed in the terminal field of mossy fibres 10-60 days after intraperitoneal injection of kainic acid. These slow but persistent increases in immunoreactivity were accompanied by markedly enhanced expression of neurokinin B mRNA in the granule cells and in hilar interneurons adjacent to the granule cell layer. These changes were preceded by transient increases in neurokinin B mRNA and immunoreactivity in CA1 pyramidal cell layer two and 10 days after kainic acid, which, however, subsided later on. Pentylenetetrazol kindling caused similar increases in neurokinin B mRNA expression in granule cells and in CA1 pyramidal cells, but not in hilar interneurons. In CA1, increased neurokinin B message was present two days after termination of the kindling procedure but not after 10 days. Sixty days after kainic acid injection, neurokinin B immunoreactivity extended to the inner-third of the molecular layer of the dentate gyrus. After pentylenetetrazol kindling, a neurokinin B-immunoreactive band was observed in the infrapyramidal region of CA3. Lesions of the dentate granule cells by local injection of colchicine in kainic acid-treated rats abolished the supragranular neurokinin B-positive staining, whereas it was almost unchanged after transection of the ventral hippocampal commissure. These observations suggest that neurokinin B immunoreactivity may be located in ipsilateral mossy fibres undergoing collateral sprouting to the inner molecular layer or to the infrapyramidal region in CA3, respectively. Preprotachykinin A mRNA, which encodes for neurokinin A and substance P, and substance P immunoreactivity were not changed in the hippocampus of epileptic rats compared with untreated animals. The observed changes in neurokinin B immunoreactivity and mRNA indicate that specific functional and morphological changes may be induced in hippocampal neurons by recurrent limbic seizures.
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PMID:Limbic seizures cause pronounced changes in the expression of neurokinin B in the hippocampus of the rat. 127 53

Our understanding of the pathophysiological mechanisms underlying the childhood epilepsies is rudimentary at this time. However, results of recent studies in animal models have lead to a number of important hypotheses concerning age-dependent alterations in seizure susceptibility. In area CA3 of hippocampus it appears that during a critical period when this brain area is particularly prone to electrographic seizures, an overabundance of recurrent excitatory synapses may exist. At the same time the synapses themselves appear to be functionally different than their mature counterpart. Age-dependent differences in the properties of postsynaptic NMDA receptors seem to contribute to enhanced seizure susceptibility. In recent years significant progress has been made in unravelling the fundamental processes that underlie the formation of connections between developing neurons. Over-production of early-formed axon collaterals appears to be common-place in the CNS. Moreover, the selection of appropriate patterns of connectivity appear to be dependent in large part on the patterning of neurophysiologic activity. In this regard the NMDA receptor seems to play a pivotal role in synapse consolidation. Based on these observations and the central role recurrent excitation appears to play in hippocampal seizures, it seems entirely plausible that excessive abnormal neuronal discharging that occurs during seizures early in life could result in the consolidation of abnormal numbers of recurrent excitatory synapses. This miswiring of hippocampal networks might be responsible for the marked seizure susceptibility into adulthood and might even contribute to complex partial epilepsy in individuals with a history of childhood seizures.
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PMID:The ontogeny of hippocampal local circuits and focal epileptogenesis. 128 4

To examine the neurotoxic effects of domoic acid, an amnesic shellfish toxin, electroencephalographic and behavioural experiments were conducted on 38 rats. Injection of domoic acid (0.5-1.0 mg/kg intravenously, or 0.04-0.08 microgram intraventricularly) caused seizure discharges in the hippocampus, tonic-clonic convulsions, and death within a few days. Convulsions and ensuing death were prevented by diazepam. Animals pretreated with diazepam (5 mg/kg, ip) tolerated intraventricular dose of domoic acid 0.4 microgram, but showed a loss of pyramidal neurons mainly in the CA3, CA4, and a part of CA1 areas of the dorsal hippocampus. Learning of a radial maze task was severely impaired in naive rats after intraventricular injection of domoic acid (and diazepam, ip). In the animals previously trained on the maze task, domoic acid interfered with relearning of the same task. These effects appear similar to those of kainic acid and are analogous to the symptoms observed in humans who ingested mussels tainted with domoic acid.
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PMID:Neural and behavioural effects of domoic acid, an amnesic shellfish toxin, in the rat. 128 34

Seizure-sensitive (SS) and seizure-resistant (SR) Mongolian gerbils were used for three experiments. In the first experiment, GABAergic neurons and terminals in the dentate gyrus were localized with GAD immunocytochemistry. GAD-positive puncta adjacent to cell bodies of GABAergic pyramidal basket cells were counted in light microscopic preparations. The pyramidal basket cells of SS gerbils displayed a significant threefold increase in the number of GAD-positive puncta associated with their cell bodies as compared to those from SR gerbils. These data indicate that the number of GABAergic synapses with pyramidal basket cell bodies in the dentate gyrus was greater in SS gerbils. An electron microscopic (EM) analysis of GAD immunocytochemical preparations showed GAD-positive axon terminals forming symmetric synapses with GAD-positive basket cell bodies. However, numerous terminals forming symmetric axosomatic synapses with basket cells were not immunopositive, and other synapses formed by terminals were not classified because reaction product in the cell bodies obscured postsynaptic densities. Therefore, routine EM preparations were analyzed for symmetric and asymmetric axosomatic synapses on pyramidal basket cells and granule cells of SS and SR gerbils. The data obtained from these preparations showed that the pyramidal basket cells of SS gerbils had a selective increase in the number of symmetric synapses per 10 microns of soma as compared to those of the SR gerbils. In contrast, the granule cells did not show any significant difference in the number of either symmetric or asymmetric axosomatic synapses between SS and SR gerbils. These results indicate that pyramidal basket cell bodies of SS gerbils have more inhibitory synapses than do those of SR gerbils. The third experiment used SS gerbils with lesions of the perforant pathway that stopped seizure activity (Ribak, C. E., and S. U. Khan (1987) The effects of knife cuts of hippocampal pathways on epileptic activity in the seizure-sensitive gerbil. Brain Res. 418:251-260). The percentage of axon terminal area occupied by synaptic vesicles and their packing density was determined in CA3 mossy fiber boutons and compared for lesioned and nonlesioned SS gerbils. The mossy fibers of nonlesioned SS gerbils showed a depletion of synaptic vesicles consistent with the previous results of Peterson et al. (Peterson, G. M., C. E. Ribak, and W. H. Oertel (1985) A regional increase in the number of hippocampal GABAergic neurons and terminals in the seizure-sensitive gerbil. Brain Res. 340:384-389).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Morphological evidence for altered synaptic organization and structure in the hippocampal formation of seizure-sensitive gerbils. 130 87

Following lesions of the fimbria-fornix, there is a time-dependent increase in interictal spikes and seizure susceptibility. This may result from sprouting of local excitatory and inhibitory circuits in response to the loss of subcortical and commissural innervation of the hippocampal formation. We used receptor autoradiography to examine the density of N-methyl-D-aspartate (NMDA)-sensitive L-[3H]glutamate and [3H]-kainate (KA) binding sites in the hippocampal formation at 5 days, 3 months, and 1 year following bilateral aspiration lesions of the fimbria-fornix. At 5 days post-lesion, the CA3 and CA1 strata radiatum and oriens displayed a decrease (20-42%, P less than 0.01) in NMDA-sensitive L-[3H]glutamate binding. The initial decrease was followed by a moderate recovery at later time points but was still evident at 1 year postlesion. This may reflect a lesion-induced turnover of synaptic complexes, down-regulation of postsynaptic receptors, or loss of presynaptic receptors. Five days following fimbria-fornix lesion there was also a decrease (13-15%, P less than 0.05) in [3H]KA binding in CA3 strata radiatum and pyramidale. However, at 3 months postlesion KA receptor density was elevated by 29-33% (P less than 0.01) in the outer molecular layer of the dentate gyrus with no significant change in binding to the inner molecular layer. By 1 year postlesion, the density of [3H]KA binding sites was not significantly different from that observed in control animals of the same age. The increase in KA receptor density in the outer molecular layer 3 months after fimbria-fornix lesion may reflect sprouting of the perforant path input or mossy fibers to this region and contribute to the increase in interictal spikes and seizures susceptibility.
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PMID:Alterations in [3H]kainate and N-methyl-D-aspartate-sensitive L-[3H]-glutamate binding in the rat hippocampal formation following fimbria-fornix lesions. 131 Apr 74

Small unilateral electrolytic lesions placed in the hilus of the dentate gyrus produce limbic seizures. We have investigated the effects of these hilar lesions on the levels of the mRNAs encoding for 3 neurotrophic factors (NTF): nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT3). 'In situ' hybridization histochemistry with synthetic oligonucleotides was used to analyze their mRNA distribution and levels. In agreement with previously published data (Science, 245 (1989) 758-761), NGF mRNA was found bilaterally, quickly and transiently increased in granule cells of the dentate gyrus. Only 2 h after the onset of limbic seizures, mRNA levels for BDNF were also found to be dramatically elevated in both sides of the hippocampus, reaching a maximum 30-fold increase in the granule cell layer of the dentate gyrus 5 h after the lesion. Moreover, increased levels of this mRNA were also been found in the pyramidal layer of the CA3 (5-fold) and CA1 (15-fold) hippocampal fields. In contrast, NT3 mRNA was found to be clearly and bilaterally decreased in dentate gyrus granule cells, reaching 5- to 6-fold decreased levels at 12 h after lesion. Taken together, these results clearly show a different regulation of neurotrophic factors genes (NGF, BDNF and NT3) expression in the different hippocampal fields, as a consequence of seizure-producing hilar lesions.
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PMID:Limbic seizures induce a differential regulation of the expression of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3, in the rat hippocampus. 131 16

Systemic injection of kainic acid (KA) does not cause neuronal pathology in limbic structures in rat brain prior to postnatal day (PND) 21. The present study tested if the development of the pathogenic response is associated with the maturation of a link between seizure activity and polyamine metabolism. Pathology was assessed with histological techniques and with the binding of [3H]Ro5-4864, a ligand for the peripheral type benzodiazepine binding sites (PTBBS), a marker of glial cell proliferation. In agreement with previous results, peripherally administered kainate at doses sufficient to induce intense behavioral seizures produced a loss of Nissl staining in hippocampus after PND 21 but not at earlier ages. The pattern of neuronal damage observed after PND 21 resembled that found in adult animals: extensive losses of Nissl staining in area CA3 of hippocampus and in piriform cortex, more modest effects in CA1 and sparing of the granule cells of the dentate gyrus. Similarly, no increase in [3H]Ro5-4864 binding as a result of KA administration was observed in hippocampus and piriform cortex until PND 21. Ornithine decarboxylase (ODC) activity and putrescine levels were high in the neonatal brain and decreased to reach adult values by PND 21. KA-induced seizure activity did not significantly alter both variables until PND 21. After PND 21, ODC activity and putrescine levels markedly increased 16 h after KA-induced seizure activity in hippocampus and piriform cortex. The magnitude of the effects increased between PND 21 and PND 30, at which point the changes in both parameters were comparable to those found in adults. Polyamines stimulate the activity of the calcium-dependent proteases calpain in brain fractions and may increase calpain-mediated proteolysis in situ. In accord with this, kainate-induced breakdown of spectrin, a preferred substrate of calpain, measured 16 h after KA injection followed a developmental curve parallel to that for kainate-induced increases in putrescine levels. These results indicate that the onset of vulnerability to seizure activity triggered by kainic acid is correlated with the development of an ODC/polyamine response to the seizures and further support a critical role for the ODC/polyamine pathway in neuronal pathology following a variety of insults.
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PMID:Seizure activity-induced changes in polyamine metabolism and neuronal pathology during the postnatal period in rat brain. 133 Mar 69

A brief application of high K+ or excitatory amino acids (i.e. kainic acid) generated repetitive synchronized burst that persisted for the duration of the application, in the CA3 field. Once excitability has been enhanced, further stimulation of various inputs evoked burst instead the typical excitatory postsynaptic potential--inhibitory postsynaptic potential sequence evoked in control conditions. These long-lasting changes in synaptic efficacy involved the activation of glutamate receptors of N-methyl-D-aspartate (NMDA) subtype. A brief period of hyperactivity (i.e. kindling of limbic pathways or administration of kainic acid) also resulted in a more delayed synaptic remodeling, notably of hippocampal mossy fibers (i.e. the axons of granule cells that mostly contact the apical dendrites of CA3 pyramidal neurons). Thus mossy fibers sprouted and made multiple ectopic asymmetrical synapses with spines of both granule cells dendrites and basilar dendrites of CA3 pyramidal cells. Finally, sprouting of mossy fibers was associated with a significant rise in the density of kainic acid binding sites (fmol/mg tissue) in the aberrantly innervated zones: the inner third of molecular layer and the stratum oriens of CA3. Saturation studies revealed that this rise did not significantly affect the affinity (Kd values) but the Bmax. In conclusion, brief seizure episodes produced in the hippocampus remarkably long-lasting changes in synaptic efficacy; synaptic density and the mean density of excitatory amino acid receptors of non-NMDA subtype. The role that such plastic changes may play in the permanence of the epilepsy is finally discussed.
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PMID:Long-term potentiation and sprouting of mossy fibers produced by brief episodes of hyperactivity. 133 65


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