UMLS:C0036572 - FACTA Search

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

Hippocampal fast ripples (FRs) have been associated with seizure onset in both human and experimental epilepsy. To characterize the mechanisms underlying FR oscillations (200-600 Hz), we studied activity of single neurons and neuronal networks in rat hippocampal slices in vitro. The correlation between the action potentials of bursting pyramidal cells and local field potential oscillations suggests that synchronous onset of action potential bursts and similar intrinsic firing patterns among local neurons are both necessary conditions for FR oscillations. Increasing the fidelity of individual pyramidal cell spike train timing by blocking accommodation dramatically increased FR amplitude, whereas blockade of potassium conductances decreased the fidelity of action potential timing in individual pyramidal cell action potential bursts and decreased FR amplitude. Blockade of ionotropic glutamate receptors desynchronized onset of action potential bursts in individual pyramidal cells and abolished fast ripples. Thus, synchronous burst onset mediated by recurrent excitatory synaptic transmission and similar intrinsic spike timing mechanisms in neighboring pyramidal cells are necessary conditions for FR oscillations within the hippocampal network.
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PMID:Mechanisms of fast ripples in the hippocampus. 1547 Jan 56

Hippocampal specimens resected to cure medically intractable temporal lobe epilepsy (TLE) provide a unique possibility to study functional consequences of morphological alterations. One intriguing alteration predominantly observed in cases of hippocampal sclerosis is an uncommon network of granule cells monosynaptically interconnected via aberrant supragranular mossy fibers. We investigated whether granule cell populations in slices from sclerotic and nonsclerotic hippocampi would develop ictaform activity when challenged by low-frequency hilar stimulation in the presence of elevated extracellular potassium concentration (10 and 12 mm) and whether the experimental activity differs according to the presence of aberrant mossy fibers. We found that ictaform activity could be evoked in slices from sclerotic and nonsclerotic hippocampi (27 of 40 slices, 14 of 20 patients; and 11 of 22 slices, 6 of 12 patients, respectively). However, the two patient groups differed with respect to the pattern of ictaform discharges and the potassium concentration mandatory for its induction. Seizure-like events were already induced with 10 mm K+. They exclusively occurred in slices from sclerotic hippocampi, of which 80% displayed stimulus-induced oscillatory population responses (250-300 Hz). In slices from nonsclerotic hippocampi, atypical negative field potential shifts were predominantly evoked with 12 mm K+. In both groups, the ictaform activity was sensitive to ionotropic glutamate receptor antagonists and lowering of [Ca2+]o. Our results show that, in granule cell populations of hippocampal slices from TLE patients, high K+-induced seizure-like activity and ictal spiking coincide with basic electrophysiological abnormalities, hippocampal sclerosis, and mossy fiber sprouting, suggesting that network reorganization could play a crucial role in determining type and threshold of such activity.
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PMID:Stimulus and potassium-induced epileptiform activity in the human dentate gyrus from patients with and without hippocampal sclerosis. 1554 57

Gamma-aminobutyric acid (GABA), one of the main inhibitory neurotransmitters in the brain, interacts with three types of receptors for GABA--GABA(A), GABA(B) and GABA(C). GABA(A) receptors, associated with binding sites for benzodiazepines and barbiturates in the form of a receptor complex, control opening of the chloride channel. When GABA binds to the receptor complex, the channel is opened and chloride anions enter the neuron, which is finally hyperpolarized. GABA(B) receptors are metabotropic, linked to a cascade of second messengers whilst the physiological meaning of ionotropic GABA(C) receptors, mainly located in the retina, is generally unknown. Novel antiepileptic drugs acting selectively through the GABA-ergic system are tiagabine and vigabatrin. The former inhibits neuronal and glial uptake of GABA whilst the latter increases the synaptic concentration of GABA by inhibition of GABA-aminotransferase. Gabapentin, designed as a precursor of GABA easily entering the brain, was shown to increase brain synaptic GABA. This antiepileptic drug also decreases influx of calcium ions into neurons via a specific subunit of voltage-dependent calcium channels. Conventional antiepileptics generally inhibit sodium currents (carbamazepine, phenobarbital, phenytoin, valproate) or enhance GABA-ergic inhibition (benzodiazepines, phenobarbital, valproate). Ethosuximide, mainly controlling absences, reduces calcium currents via T-type calcium channels. Novel antiepileptic drugs, mainly associated with an inhibition of voltage-dependent sodium channels are lamotrigine and oxcarbazepine. Since glutamate-mediated excitation is involved in the generation of seizure activity, some antiepileptics are targeting glutamatergic receptors--for instance, felbamate, phenobarbital, and topiramate. Besides, they also inhibit sodium currents. Zonisamide, apparently sharing this common mechanism, also reduces the concentration of free radicals. Novel antiepileptic drugs are better tolerated by epileptic patients and practically are devoid of important pharmacokinetic drug interactions.
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PMID:Mechanisms of action of antiepileptic drugs. 1563 74

We have previously demonstrated that repeated exposure of adult rat hippocampal slices to brief episodes of hypoxia induce a sustained decrease in the threshold of stimulus-evoked population spike discharges in CA1 pyramidal neurons [O. Godukhin, A. Savin, S. Kalemenev, S. Levin, Neuronal hyperexcitability induced by repeated brief episodes of hypoxia in rat hippocampal slices: involvement of ionotropic glutamate receptors and L-type Ca2+ channels, Neuropharmacology 42 (2002) 459-466, S.V. Kalemenev, A.V. Savin, S.G. Levin, O.V. Godukhin, Long-term potentiation and epileptiform activity induced by brief hypoxic episodes in CA1 area of the rat hippocampal slices. Russ. Physiol. J. 86 (2000) 1676-1681]. In the present study, using the above-mentioned in vitro model of epileptogenesis, we compared the developmental changes in hypoxia-induced hyperexcitability of CA1 neuronal network in the rat hippocampal slices prepared from three age rat groups: postnatal days (P) 13-14 (young), P60-70 (adult) and P600-650 (old). Furthermore, we were interested in learning about an age dependence of the hypoxia-induced changes in the efficacies of glutamatergic transmission and paired-pulse inhibition in CA3-CA1 synapses that may underlie ontogenetic differences in seizure susceptibility in hippocampal network. The principal results of this work are summarized as follow. In comparison with P60-70 hippocampal slices, CA1 pyramidal neurons in P13-14 and P600-650 slices showed intrinsically (without repeated brief hypoxa) an increased propensity to generate epileptiform stimulus-evoked population spike discharges. However, in contrast to adult and old animals, repeated brief episodes of hypoxia are incapable to induce a sustained decrease in the threshold of stimulus-evoked population spike discharges in CA1 pyramidal neurons of hippocampal slices prepared from of P13-14 rats, though they transform paired-pulse inhibition to paired-pulse facilitation and induce hypoxic LTP in CA3-CA1 synapses. The role of some other factors in the developmental changes in hyperexcitability of CA1 pyramidal neurons in response to repeated brief episodes of hypoxia is discussed.
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PMID:Developmental changes in hyperexcitability of CA1 pyramidal neurons induced by repeated brief episodes of hypoxia in the rat hippocampal slices. 1572 80

Fast oscillations at approximately 200 Hz, termed ripples, occur in the hippocampus and cortex of several species, including humans, and are thought to play a role in physiological (e.g., sensory information processing or memory consolidation) and pathological (e.g., seizures) processes. Blocking gamma-aminobutyric acid type A (GABA(A)) receptor-mediated inhibition represents one of the most often used models of epileptiform discharge. Here we found that bath application of the GABA(A) receptor antagonist picrotoxin (50 microM) to mouse hippocampus-entorhinal cortex slices induced spontaneous epileptiform activity (duration 536.6 +/- 146.1 msec, mean +/- SD; interval of occurrence 14.8 +/- 3.3 sec, n = 12) with two distinct phases of discharge; the first was characterized, in the dentate gyrus only, by high-frequency, field oscillations (ripples) at 206.3 +/- 23.4 Hz (n = 12), whereas the second component corresponded to afterdischarges in the theta range frequency. Ripples, which were also recorded in "minislices" only of the dentate gyrus, were unaffected by application of the mu-opioid receptor agonist (D-Ala2-N-Me-Phe,Gly-ol)enkephalin (10 microM; n = 6) or the N-methyl-D-aspartate (NMDA) receptor antagonist 3-(2-carboxy-piperazine-4-yl)-propyl-l-phosphonate (10 microM; n = 5). In contrast, the non-NMDA glutamatergic receptor antagonist 6-cyano-7-nitro-quinoxaline-2,3-dione (10 microM; n = 5) completely blocked all picrotoxin-induced activities. In addition, application of the GABA(B) receptor agonist baclofen (0.01-0.5 microM; n = 6) dose dependently and reversibly abolished all picrotoxin-induced activities. We also found that application of the gap-junction decouplers carbenoxolone (0.2-0.5 mM; n = 6) or octanol (0.2-0.5 mM; n = 3) blocked the second phase while leaving ripples unchanged. These findings demonstrate that the disinhibited dentate gyrus can generate ripple activity at approximately 200 Hz that is contributed by ionotropic glutamatergic mechanisms and is not dependent on either GABA(A) receptor-mediated or gap-junction mechanisms.
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PMID:Ripple activity in the dentate gyrus of dishinibited hippocampus-entorhinal cortex slices. 1574 60

Gliosis is a hypertrophic and hyperplastic response to many types of central nervous system injury, including trauma, stroke, seizure, as well as neurodegenerative and demyelinating disorders. Reactive astrocytes, a major component of the glial scar, express molecules that can both inhibit and promote axonal regeneration. ATP, which is released upon traumatic injury, hypoxia, and cell death, contributes to the gliotic response by binding to specific cell surface astrocytic P2 nucleotide receptors and evoking characteristic features of gliosis such as increased expression of glial fibrillary acidic protein (GFAP), generation and elongation of astrocytic processes, and cellular proliferation. Here, we review recent studies that demonstrate that (1) metabotropic, P2Y, and ionotropic, P2X, receptors expressed in astrocytes are coupled to protein kinase signaling pathways that regulate cellular proliferation, differentiation, and survival such as ERK and protein kinase B/Akt and (2) these P2 receptor/protein kinase cascades are activated after trauma induced by mechanical strain. We suggest that P2 receptor/protein kinase signaling pathways might provide novel therapeutic targets to regulate the formation of reactive astrocytes and the production of molecules that affect axonal regeneration and neurodegeneration.
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PMID:Signaling from P2 nucleotide receptors to protein kinase cascades induced by CNS injury: implications for reactive gliosis and neurodegeneration. 1595 14

The glutamatergic granule cells of the dentate gyrus transiently express GABAergic markers after seizures. Here we show that when this occurs, their activation produces (i) GABA(A) receptor-mediated synaptic field responses in CA3, with the physiological and pharmacological characteristics of mossy fibre transmission, and (ii) GABA(A) receptor-mediated collateral inhibition. Control hippocampal slices present, on stimulation of the dentate gyrus, population responses in stratum lucidum, which are blocked by ionotropic glutamate receptor antagonists. By contrast, in slices from rats subjected to seizures in vivo, dentate activation additionally produces GABA(A) receptor-mediated field synaptic responses in the presence of glutamate receptor antagonists. One-dimensional current source density analysis confirmed the spatial coincidence of the glutamatergic and GABAergic dendritic currents. The GABA(A) receptor-mediated field responses show frequency-dependent facilitation and strong inhibition during activation of metabotropic glutamate receptors. In the presence of glutamate receptor blockers, a conditioning pulse delivered to one site of the dentate gyrus inhibits the population synaptic response and the afferent volley provoked by the activation of a second site, in a bicuculline-sensitive manner. In accordance with this, antidromic responses evoked by mossy fibre activation were enhanced by perfusion of bicuculline. Our results suggest that, for GABA receptor-dependent field potentials to be detected, a considerable number of boutons of a well-defined GABAergic pathway should simultaneously release GABA to act on a large number of receptors. Therefore, putative GABA release from the mossy fibres acts on pre- and postsynaptic sites to affect hippocampal activity at the network level after seizures.
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PMID:The GABAergic projection of the dentate gyrus to hippocampal area CA3 of the rat: pre- and postsynaptic actions after seizures. 1600 42

Isoniazid (INH) has neurotoxic effects such as seizure, poor concentration, subtle reduction in memory, anxiety, depression and psychosis. INH-induced toxic effects are thought to be through increased oxidative stress, and these effects have been shown to be prevented by antioxidant therapies in various organs. Increased oxidative stress may be playing a role in these neurotoxic effects. N-methyl D-aspartat receptors (NMDA) are a member of the ionotropic group of glutamate receptors. These receptors are involved in a wide variety of processes in the central nervous system including synaptogenesis, synaptic plasticity, memory and learning. Erdosteine is a potent antioxidant and mucolytic agent. We aimed to investigate adverse effects of INH on rat hippocampal NMDAR receptors, and to elucidate whether erdosteine prevents possible adverse effects of INH. In the present study, compared to control group, NMDAR2A (NR2A) receptors were significantly decreased and malondialdehyde (MDA), end product of lipid peroxidation, production was significantly increased in INH-treated group. On the other hand, administration of erdosteine to INH-treated group significantly increased NR2A receptors and decreased MDA production. In conclusion, decreasing NR2A receptors in hippocampus and increasing lipid peroxidation correlates with the degree of oxidative effects of INH and erdosteine protects above effect of INH on NR2A receptors and membrane damage due to lipid peroxidation by its antioxidant properties.
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PMID:The effects of isoniazid on hippocampal NMDA receptors: protective role of erdosteine. 1613 24

A paroxysmal depolarization shift (PDS) has been suggested to be a hallmark for epileptic activity in partial-onset seizures. By monitoring membrane potentials and currents in pairs of pyramidal neurons and astrocytes with dual patch-clamp recording and exocytosis of vesicles from astrocytes with two-photon laser scanning microscopy in hippocampal slices, we found that infusion of inositol 1,4,5-trisphosphate (IP(3)) into astrocytes by patch pipettes induced astrocytic glutamate release that triggered a transient depolarization (TD) and epileptiform discharges in CA1 pyramidal neurons. The TD is due to a tetrodotoxin (TTX)-insensitive slowly decaying transient inward current (STC). Astrocytic glutamate release simultaneously triggers both the STC in pyramidal neurons and a transport current (TC) in astrocytes. The neuronal STC is mediated by ionotropic glutamate receptors leading to the TD and epileptiform discharges; while the astrocytic TC is a glutamate reuptake current resulting from transporting released glutamate into the patched astrocyte. Fusion of a large vesicle in astrocytes was immediately followed by an astrocytic TC, suggesting that the fused vesicle contains glutamate. Both fusion of large vesicles and astrocytic TCs were blocked by tetanus toxin (TeNT), suggesting that astrocytic glutamate release is via SNARE-dependent exocytosis of glutamate-containing vesicles. In the presence of TTX, the epileptogenic reagent, 4-AP, also induced similar neuronal STCs and astrocytic TCs, suggesting that astrocytic glutamate release may play an epileptogenic role in initiation of epileptic seizures under pathological conditions. Our study provides a novel mechanism, astrocytic release of glutamate, for seizure initiation.
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PMID:Astrocytic glutamate release-induced transient depolarization and epileptiform discharges in hippocampal CA1 pyramidal neurons. 1616 34

The entorhinal cortex (EC) provides the predominant excitatory drive to the hippocampal CA1 and subicular neurones in chronic epilepsy. Here we analysed the effects of one-sided lateral EC (LEC) and temporoammonic (alvear) path lesion on the development and properties of 4-aminopyridine-induced seizures. Electroencephalography (EEG) analysis of freely moving rats identified that the lesion increased the latency of the hippocampal seizure significantly and decreased the number of brief convulsions. Seizure-induced neuronal c-fos expression was reduced in every hippocampal area following LEC lesion. Immunocytochemical analysis 40 days after the ablation of the LEC identified sprouting of cholinergic and calretinin-containing axons into the dentate molecular layer. Region and subunit specific changes in the expression of ionotropic glutamate receptors (iGluRs) were identified. Although the total amount of AMPA receptor subunits remained unchanged, GluR1(flop) displayed a significant decrease in the CA1 region. An increase in NR1 and NR2B N-methyl-d-aspartate (NMDA) receptor subunits and KA-2 kainate receptor subunit was identified in the deafferented layers of the hippocampus. These results further emphasize the importance of the lateral entorhinal area in the spread and regulation of hippocampal seizures and highlight the potential role of the rewiring of afferents and rearrangement of iGluRs in the dentate gyrus in hippocampal convulsive activity.
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PMID:Lateral entorhinal cortex lesions rearrange afferents, glutamate receptors, increase seizure latency and suppress seizure-induced c-fos expression in the hippocampus of adult rat. 1618 16

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