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

Thalamocortical circuits are recognized as the main elements involved in the genesis of synchronized oscillations typical of certain generalized seizures. We addressed the capability of thalamic disinhibition to generate synchronized oscillations in neocortex. Microdialysis was used to infuse GABA(A) and GABA(B) receptor antagonists directly into the thalamus of anesthetized rats while recording cortical field potentials from 16 sites aligned perpendicular to the cortical surface, using 100 microm spaced linear array silicon probes. The results demonstrate that block of thalamic GABA(A) receptors induces continuous 3 Hz discharges in neocortex and that thalamic GABA(B) receptors mediate this activity. Also, during thalamic disinhibition sporadic long-lasting discharges at 12 Hz occur that do not depend on GABA(B) receptors. Current source density analysis of these activities revealed that the dynamics of sinks and sources for the 3 and 12 Hz discharges was quite distinct, in a way that suggests a different active involvement of the neocortex. The results indicate that intrathalamic inhibitory processes play an essential role in the generation of neocortical synchronized oscillatory activity that may be related to certain forms of generalized seizures.
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PMID:Neocortical synchronized oscillations induced by thalamic disinhibition in vivo. 1047 20

The presence of paroxysmal discharges in the epileptic human dentate gyrus provides a physiologic basis for hyperexcitability that may initiate seizure discharges during the development of epilepsy. Although these responses can occur with single orthodromic stimulation, data obtained under conditions that weaken synaptic inhibition (e.g., 1 Hz stimulation or bicuculline disinhibition) suggest that paroxysmal discharges may be a more common feature of tissue from temporal lobe epileptic patients than has been reported previously. Hilar cell loss and weakened synaptic inhibition may provide conditions favorable for the activation of N-methyl-D-aspartate acid (NMDA) receptors that would allow triggering of paroxysmal discharges that normally never are evoked in dentate granule cells in nonepileptic humans. As the dentate gyrus in normal animal tissue is not susceptible to intrinsic bursting behavior and is characterized by a relatively short duration excitatory postsynaptic potential even under pharmacologic disinhibition, paroxysmal discharges in the epileptic human dentate gyrus may provide an important clue to understanding the prerequisite conditions for seizure discharge.
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PMID:Physiological and anatomical correlates of the human dentate gyrus: consequences or causes of epilepsy. 1051 63

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors are key mediators of seizure spread in the nervous system and represent promising targets for antiepileptic drugs. There is emerging evidence that AMPA receptors may play a role in epileptogenesis and in seizure-induced brain damage. This evidence suggests that AMPA receptor antagonists could have broad utility in epilepsy therapy. Regional, developmental, and disease-associated variations in AMPA receptors produced by differential expression of AMPA receptor subunits and variations in posttranscriptional processing, including alternative splicing and pre-mRNA editing, provide a diversity of functionally distinct AMPA receptor isoforms that allow opportunities for selective drug targeting. Four types of AMPA receptor antagonist are discussed in this chapter: (a) competitive AMPA recognition site antagonists, including those of the quinoxalinedione and newer nonquinoxalinedione classes, (b) 2,3-benzodiazepine noncompetitive (allosteric) antagonists, (c) desensitization enhancing antagonists, exemplified by SCN-, and (d) antagonists of Ca(2+)-permeable AMPA receptors, including polyamine amide arthropod toxins and their synthetic analogues. Competitive and noncompetitive AMPA receptor antagonists are broad-spectrum anticonvulsants in animal seizure models. Their effectiveness and safety for humans remain to be determined. There is evidence that these antagonists can potentiate the antiseizure activity of N-methyl-D-aspartate (NMDA) receptor antagonists and conventional antiepileptic drugs. This evidence suggests that the preferred use of AMPA receptor antagonists may be in combination therapies. Agents that enhance desensitization may have advantages in comparison with other AMPA receptor antagonists to the extent that they preferentially block high-frequency synaptic signaling and avoid depressing AMPA receptors on interneurons, which would lead to disinhibition and enhanced excitability. Evidence has accumulated that Ca(2+)-permeable AMPA receptors (those lacking the edited GluR2 subunit) may play a role in epileptogenesis and the brain damage occurring with prolonged seizures. Because Ca(2+)-permeable AMPA receptors are predominately expressed in gamma-aminobutyric acid (GABA)ergic interneurons, it is hypothesized that some forms of epilepsy might be caused by reduced GABA inhibition resulting from Ca(2+)-permeable AMPA receptor-mediated excitotoxic death of interneurons. It is further proposed that drugs that selectively target Ca(2+)-permeable AMPA receptors might have antiepileptogenic and neuroprotective properties. Certain polyamine toxins and their analogues are channel-blocking AMPA receptor antagonists that selectively inhibit Ca(2+)-permeable AMPA receptors. These substances might give clues to the development of such antagonists.
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PMID:AMPA receptors in epilepsy and as targets for antiepileptic drugs. 1051 78

Membrane potential of ventral respiratory group neurons as well as inspiratory-related cranial (hypoglossal) and spinal (C(1)-Th(4)) nerve activities were analysed in brainstem-spinal cord preparations from neonatal rats. Block of Cl(-)-mediated inhibition with bicuculline (plus strychnine) affected neither rhythmic depolarizations nor spike discharge in 23 of 30 ventral respiratory group cells. In the other seven neurons, block of inhibitory postsynaptic potentials evoked pronounced depolarizations and spike discharge that was synchronous with seizure-like spinal nerve activity. Respiratory hypoglossal nerve activity persisted after transection at the spinomedullary junction, whereas spinal rhythm was blocked. After transection, the moderate bicuculline-evoked seizure-like perturbation of hypoglossal nerve activity was abolished and rhythmic ventral respiratory group neuron activity was not disturbed, whereas epileptiform discharge persisted in spinal nerves. The seizure-like nerve activity and depolarization of the minor subpopulation of perturbed ventral respiratory group neurons were reversed by either adenosine or the A(1) adenosine receptor agonist 2-chloro-N(6)-cyclopentyladenosine. The A(2) receptor agonist CGS 21860 had no effect. In control preparations, inspiratory nerve activity and membrane potential fluctuations (29 of 35 cells) were not changed by adenosine, 2-chloro-N(6)-cyclopentyladenosine or CGS 21860. In the other six cells, adenosine evoked a hyperpolarization (<10 mV) with no major change in input resistance. The anticonvulsant effects of adenosine and 2-chloro-N(6)-cyclopentyladenosine were antagonized by the A(1) adenosine receptor blocker 8-cyclopentyl-1,3-dipropylxanthine. After pre-incubation with 8-cyclopentyl-1,3-dipropylxanthine, bicuculline also evoked seizure-like discharge in the hypoglossal nerve. The results indicate that seizure-like spinal motor output of the respiratory network upon block of Cl(-)-mediated inhibition is caused by disinhibition of spinal neuronal networks with afferent connections to the ventral respiratory group. Presynaptic A(1) adenosine receptors exert an anticonvulsant action on the disinhibited spinal motor network, but have no depressing effect per se on the isolated medullary respiratory network.
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PMID:Anticonvulsant A(1) receptor-mediated adenosine action on neuronal networks in the brainstem-spinal cord of newborn rats. 1068 76

The purpose of this study was to identify cellular and synaptic properties of neurons in a small region within the anterior piriform cortex (aPC), termed the area tempestas (AT), responsible for triggering forebrain seizures in rats. Using a brain slice preparation, we performed whole-cell patch recordings from neurons in the regions overlapping the functionally defined AT. Local electrical stimulation activated synaptic inputs to neurons in these regions, collectively termed the deep aPC (daPC). Synaptic inputs were blocked by selective ionotropic glutamate receptor antagonists. Excitatory bursts were evoked from 59% of daPC neurons as the stimulus intensity was raised above a precise threshold. Secondary bursts (6-15 Hz) occurred in 34% of daPC neurons. Evoked bursts were synaptically driven, as they were blocked by TTX (1 microM) or 2, 3-dihydroxy-6-nitro-7-sulfamoyl-benzo(f)quinoxaline (NBQX, 1 microM), but not by inclusion of cesium and N-(2, 6-dimethylphenylcarbamoylmethyl) triethylammonium (QX-314) in the internal patch solution. Neither augmentation of excitatory nor suppression of inhibitory transmission were required to evoke bursts from daPC neurons. However, bicuculline (20 microM) lowered the threshold intensity for evoking discharges and increased the incidence and duration of evoked bursts, indicating active inhibitory control of daPC neurons. Stimulation in the daPC evoked epileptiform field potentials from layer II of the adjacent PC and bursts from layer II pyramidal neurons. This work demonstrates that synaptically dependent excitatory burst discharges can be evoked from daPC neurons without altering the balance between synaptic excitation and inhibition. Stimuli that trigger bursts in daPC neurons also generate epileptiform activity in layer II pyramidal cells, indicating that propagation of excitatory activity triggered from the daPC to the pyramidal neurons of the aPC can contribute to the initiation of seizures induced by disinhibition of the AT in vivo.
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PMID:Evoked epileptiform discharges in the rat anterior piriform cortex: generation and local propagation. 1075 67

In this study we describe the preventive effect of interruption of the supramammillohippocampal afferents on the Fos expression in the forebrain and epileptic discharges in the hippocampal electroencephalogram in rat model of kainic acid-induced limbic seizure. Little was known about the contribution of different degrees of neural activity of hippocampal principal cells to the genesis and spread of limbic seizures in the forebrain structures. Following kainic acid injection to the amygdala with or without concurrent injection of muscimol to the supramammillary nucleus, behavioral changes and electroencephalograms were observed in freely moving rats. The animals were processed for Fos immunocytochemical analysis at several time points. The latest expression of Fos at 2h was seen in hippocampal CA1-CA3, ventrolateral thalamic nuclei and mediodorsal caudate putamen, while the early Fos expression at 0.5h was seen in the piriform, entorhinal and other cortices, the thalamic midline nuclei and hypothalamic nuclei. Muscimol injection to the supramammillary nucleus prevented Fos expression in the CA1-CA3 region and reduced that in the forebrain regions with the latest Fos expression, but did not affect Fos expression in other forebrain regions with early Fos expression. This treatment also eliminated epileptic discharges and attenuated all waves in hippocampus. These findings indicate that an acute interruption of the facilitatory hypothalamic afferents by intrasupramammillary injection of muscimol may cause the inactivation of the disinhibition mechanism for hippocampal throughput at the dentate gyrus, resulting in the blockade of the genesis and spread of limbic seizures in the hippocampus.
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PMID:Interruption of supramammillohippocampal afferents prevents the genesis and spread of limbic seizures in the hippocampus via a disinhibition mechanism. 1082 27

The "disinhibition" hypothesis contends that (1) seizures begin when granule cells in the dentate gyrus of the dorsal hippocampus are disinhibited and (2) disinhibition occurs because GABAergic interneurons are excessively inhibited by other GABAergic interneurons. We tested the disinhibition hypothesis using the experimental model that inspired it-naturally epileptic Mongolian gerbils. To determine whether there is an excess of GABAergic interneurons in the dentate gyrus of epileptic gerbils, as had been reported previously, GABA immunocytochemistry, in situ hybridization of GAD67 mRNA, and the optical fractionator method were used. There were no significant differences in the numbers of GABAergic interneurons. To determine whether granule cells in epileptic gerbils were disinhibited during the interictal period, IPSPs were recorded in vivo with hippocampal circuits intact in urethane-anesthetized gerbils. The reversal potentials and conductances of IPSPs in granule cells in epileptic versus control gerbils were similar. To determine whether the level of inhibitory control in the dentate gyrus transiently decreases before seizure onset, field potential responses to paired-pulse perforant path stimulation were obtained from the dorsal hippocampus while epileptic gerbils experienced spontaneous seizures. Evidence of reduced inhibition was found after, but not before, seizure onset, indicating that seizures are not triggered by disinhibition in this region. However, seizure-induced depression of inhibition may amplify and promote the spread of seizure activity to other brain regions. These findings do not support the disinhibition hypothesis and suggest that in this model of epilepsy seizures initiate by another mechanism or at a different site.
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PMID:Testing the disinhibition hypothesis of epileptogenesis in vivo and during spontaneous seizures. 1093 73

Schizencephaly is an extremely rare congenital disease caused by abnormal neuronal migration. The etiology of schizencephaly is not established but vascular disturbance in early childhood could cause this condition. We have cared of a patient with schizencephaly. The patient was 47 year old male. He had focal motor seizure with secondary generalization. Neurological examination revealed, mild left hemiparesis, left pyramidal signs with no sensory impairment, left hemiatrophy, and mirror movement. MRI findings showed schizencephaly, open lip type(type II) in right cerebral hemisphere. His epileptic seizure was controlled by administration of sodium valproate. The possible mechanism of this mirror movement in his left hand and leg could be reorganization of non-affected brain and disinhibition on homolateral pyramidal tract in non-affected left cerebral hemisphere by the transcallosal inhibitory pathyway from affected right cerebral hemisphere. Sodium valpronate can not suppress this mirror movement.
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PMID:[A case with symptomatic epilepsy and mirror movement due to unilateral schizencephaly]. 1093 22

Evidence derived from both clinical and experimental investigations has suggested an influence of ionizing radiation on focal epileptogenicity. To better characterize this influence we applied focal ionizing radiation to a kindled epileptic focus in the rat amygdala. The right and left basolateral amygdala and right frontal cortex were implanted with concentric bipolar electrodes. Rats were kindled through a minimum of 10 stage 5 seizures by afterdischarge-threshold electrostimulation of the left amygdala, after which generalized seizure thresholds were determined prior to irradiation. The left amygdala was exposed to single-fraction central-axis doses of either 18 or 25 Gy using a beam-collimated (60)Co source (1.25 MeV). Generalized seizure thresholds were then redetermined at weekly intervals for 10 weeks and at monthly intervals for an additional 3 months. We observed no significant changes in seizure threshold during the postirradiation interval; however, we did observe persistent changes in seizure dynamics manifesting within the first week postirradiation. These consisted of an increased tendency for seizure activity to propagate into brain stem circuits during the primary ictus (i.e., "running fits") and an increased tendency for secondary convulsions to emerge postictally. These effects involving seizure dynamics have not been reported previously and appear to represent a radiation-induced disinhibition of one or more neural circuits. The disparity between these effects and earlier reports of seizure-suppressive effects resulting from analogous radiation exposures is discussed in relation to kindling and status epilepticus-induced pathogenesis within the hippocampus.
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PMID:Enhanced excitability induced by ionizing radiation in the kindled rat. 1131 62

We performed long-term video/ EEG monitoring and a single photon emission computed tomographic (SPECT) study to clarify generating mechanism of bilateral tonic motor seizures resembling seizures generated by the supplementary motor area (SMA), in patients with bilateral parietal lesions. We describe 2 patients (age 24 and 32 years), with bilateral parietal lesions. Clinically, seizures were preceded by lightning sensation in the body, followed by asymmetric tonic posturing of both hands and thrashing movements of the feet, lasting for less than 1 min. Ictal rhythmic (7-15 Hz) activity at the vertex was observed on the EEG in 1 patient. Interictal SPECT in 2 patients showed decreased blood flow in both parietal areas, consistent with bilateral parietal abnormalities on T2- and T1-weighted MRIs. Ictal SPECT in 1 patient showed increased blood flow in the right parietal and frontopolar areas. The present 2 patients had clinically asymmetric tonic seizures, most likely resulting from spreading of the ictal activity from the parietal lesions via the superior longitudinal fasciculus to the SMA. Bilateral, homologous lesions in the parietal area might cause disinhibition on the unilateral epileptogenic side.
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PMID:Asymmetric tonic seizures with bilateral parietal lesions resembling frontal lobe epilepsy. 1131 18


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