Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Quantitative autoradiography was used to study changes in high affinity (Kd = 12 nM) binding sites for kainic acid, a marker of mossy fibers, in the hippocampus of childhood epileptics. We found a highly significant increase in the density of kainate binding sites in the CA3 region and in the fascia dentata in childhood epileptics as compared to age matched controls. We suggest that anatomical plasticity occurs in the hippocampus of human epileptics as in experimental models of epilepsy. The increase in kainate binding sites may contribute to the development of epileptic seizures.
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PMID:Hippocampal plasticity in childhood epilepsy. 254 48

The time course and severity of the excitotoxic syndrome induced in rats by s.c. injection of 10 mg/kg kainic acid (KA) was modified by pretreatment with MK801, a non-competitive inhibitor of the NMDA receptor, at doses of 0.1, 1 and 10 mg/kg. A dose-dependent increase in the severity of the KA-induced electrographic (EEG) manifestations of epilepsy was seen after MK801. This consisted of an earlier appearance and higher number of EEG seizures, longer time spent in seizures, and an earlier onset of status epilepticus. In contrast, behavioral seizures were increased only in the 0.1 mg/kg MK801 group, but abolished by higher doses. On the contrary, wet dog shakes were progressively reduced with increasing doses of MK801. Four of the 9 animals receiving KA-only group and 3 of the 10 animals in the 1 and 10 mg MK801 groups were sacrificed 5 days after KA. The brain of the KA-only rats presented diffuse gross and microscopic evidence of hemorrhagic necrosis and neuronal damage; the MK801 rats showed only minimal neuronal loss in the CA3 hippocampal sector. This study demonstrates that neuronal damage and epileptiform activity can be dissociated. Furthermore, it confirms the protective effect of MK801 against neuronal damage caused by multiple factors. Lastly, it emphasizes the need for EEG monitoring in order to accurately assess any epileptic/antiepileptic effect.
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PMID:Potentiation of kainic acid epileptogenicity and sparing from neuronal damage by an NMDA receptor antagonist. 254 57

Reduction of external calcium and magnesium from 1.5 to 1.2 mM intensified potassium-induced interictal bursts, increased the likelihood of electrographic seizure occurrence in CA1, and rendered seizure initiation independent of N-methyl-D-aspartate (NMDA) receptor activation. In contrast to slices bathed in 1.5 mM divalent cations, in 1.2 mM divalents spontaneous CA1 seizures still occurred in CA1 minislices that contained at least 1500 neurons after removal of the CA3 burst generator, suggesting that divalent cations critically modulate the dependence of CA1 seizure initiation on interictal input. Since this slight reduction in external divalent cations enhanced tissue excitability, similar changes might promote epileptogenesis in situ.
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PMID:Modification of potassium-induced interictal bursts and electrographic seizures by divalent cations. 256 67

A single dose (19 mg kg-1) of triethyllead given to weanling rats produces necrosis in a small number of hippocampal pyramidal (CA3) and hilar neurons with reversible changes in the remaining neurons of this region. The sequence of events has been studied by light and electron microscopy over a period from 12 h to 14 days after dosing. Early changes resemble those previously described for trimethyltin, with the formation of characteristic tubulo-vesicular dense bodies by 12 h accompanied by vacuolation of Golgi and smooth surfaced endoplasmic reticulum (SER) elements which became generalized by 24 h. Large numbers of secondary dense bodies, formed from tubulo-vesicular dense bodies as well as from autophagosomes, were present by 48 h, whilst very little rough surfaced endoplasmic reticulum (RER) and few polyribosomes remained and vacuolation was much reduced. In those animals which did not die from seizures, the majority of hippocampal pyramidal cells were able to recover from these changes with astrocytes playing a significant role in the elimination of the dense bodies. This involved astrocytes inserting processes into the neuronal perikaryon from where the secondary dense bodies were selectively transferred into the astrocyte cytoplasm. This activity was first seen at 48 h, reached a peak at 4 days, when most CA3 neurons contained one or more astroglial intrusions and subsided soon after. The surviving neurons returned to apparent normality over the period from 3 to 7 days with a gradual return of polyribosomes. Golgi elements and RER.
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PMID:Reversible neuronal damage in hippocampal pyramidal cells with triethyllead: the role of astrocytes. 258 20

The properties of high [K+]o-induced spontaneous bursting and electrographic seizures in hippocampal slices prepared from rats subjected to kindling from either the lateral entorhinal cortex or the angular bundle were compared to those in control slices. Kindling enhanced the frequency of K+-induced burst-firing in the CA3 region and the duration of triggered bursts in the dentate gyrus, as previously reported. However, kindling had no influence on the characteristics or occurrence of electrographic seizures in the CA1 region of slices bathed in elevated [K+]o. In addition, the development of electrographic seizures in slices from control animals did not require a preconditioning period of burst input from the CA3 region.
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PMID:Effect of kindling on potassium-induced electrographic seizures in vitro. 259 18

These experiments present a model of spontaneous epileptiform activity that can be produced acutely in the urethane-anesthetized rat. Extracellular potential changes were recorded in CA1 or the dentate gyrus along with measurements of extracellular potassium ([K+]0) and calcium ([Ca2+]0) throughout 90 min of continuous stimulation to the contralateral CA3 region and for up to 4 h afterwards. During the continuous stimulation, both brain regions showed a cyclic pattern of electrographic seizures. Immediately upon stopping the stimulation, spontaneous epileptiform activity continued for up to 90 min in both CA1 and dentate gyrus. A quiescent period without electrographic activity was followed by the return of spontaneous epileptiform activity an average of 2 h after the end of stimulation. The excitability of the system was depressed after the continuous stimulation and gradually recovered during the quiescent period before the onset of the spontaneous epileptiform activity. [K+]0 increased during, not before, each seizure (both during the continuous stimulation and during the delayed spontaneous epileptiform activity) and remained elevated as long as neuronal discharges occurred. [Ca2+]0 transiently decreased with the onset of electrographic activity and never decreased before the appearance of epileptiform discharges.
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PMID:Model of spontaneous hippocampal epilepsy in the anesthetized rat: electrographic, [K+]0, and [Ca2+]0 response patterns. 261 91

The electrophysiological properties of the neural pathways between the hippocampus and the entorhinal cortex were studied intraoperatively in 31 patients undergoing anterior temporal lobectomy for medically intractable complex partial seizures. The hippocampus, removed en bloc, was studied histologically and the pathology was correlated with the electrophysiological findings. In 29 of the patients, entorhinal stimulation evoked a characteristic positive-negative potential in the hippocampus. The entorhinal-evoked hippocampal response closely resembled, or was identical to, the spontaneously occurring hippocampal interictal spike discharge. In patients with Ammon's horn sclerosis in whom there was a major loss of neurons in the hippocampal subfields CA1, CA3, and CA4, the evoked responses were of simple morphology and long latency (mean 21.9 msec to the peak of the first potential). In patients with a ganglioglioma in whom the hippocampus was histologically normal, the evoked responses were of greater complexity and shorter latency (mean 11.8 msec). Stimulation at a single entorhinal site evoked similar waveforms at different hippocampal recording sites. Conversely, stimulation at different entorhinal sites evoked similar responses at a single hippocampal recording site. Stimulation of the hippocampus evoked a potential in the entorhinal cortex and, in some instances, in the amygdala, insula, and lateral temporal cortex. These connections may produce a positive feedback loop that favors seizure generation.
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PMID:Electrophysiological connections between the hippocampus and entorhinal cortex in patients with complex partial seizures. 270 6

Spontaneous and evoked field potentials and cellular discharges were studied in the subcortically denervated hippocampus of the freely moving rat. The fimbria fornix, the ventral hippocampal commissure, and the supracallosal afferent fibers were removed by aspiration, and recordings were made 3-5 months after the lesion. Two types of spontaneous interictal spikes were observed. Type 1 interictal spike had identical depth distribution to physiological sharp waves but they were shorter in duration (less than 40 ms), larger in amplitude (greater than 2.5 mV) and population spikes were riding on the main deflection. Type 2 interictal spikes were negative in the stratum oriens and positive in the pyramidal layer and stratum radiatum of both CA1 and CA3. The amplitude of both types of interictal spikes could exceed 6 mV. We suggest that interictal spikes were initiated randomly in different subpopulations of the CA2-3 region and the location of the initiating population burst determined the polarity and amplitude of the extracellular interictal spike. Repetitive stimulation of the perforant path (5 Hz, 6 s) evoked markedly uniform afterdischarges in both intact and fimbria fornix-deprived rats. The threshold of afterdischarges was significantly lower, the seizure spread to the contralateral hippocampus was slower, and secondary afterdischarges lasted significantly longer in the lesioned rats. We suggest that under physiological conditions the electrical stability of the hippocampus is ensured by the feed-forward inhibitory action of subcortical afferents. Removal of tonic inhibitory influences and/or sprouting of local axon collaterals allows extreme synchronization and reverberation of information in the entorhinal-hippocampal-entorhinal cortex circuitry. The presence of interictal spikes and increased susceptibility to seizures for several months after the lesion offers the fimbria-fornix-deprived hippocampus a useful chronic preparation to study the mechanisms of limbic epilepsy.
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PMID:Neuronal activity in the subcortically denervated hippocampus: a chronic model for epilepsy. 271 Mar 28

Developmental alterations in GABAergic synaptic transmission were examined physiologically and biochemically in hippocampus of rats from 3 days of age to adulthood. Neither antidromic nor orthodromic stimulation could elicit identifiable inhibitory postsynaptic potentials in CA1 neurons in slices from rats 5 or 6 days of age. In contrast, at this age these stimuli result in large inhibitory postsynaptic potentials in CA3 pyramidal cells. In the latter cells orthodromic stimulation produced a brief monosynaptic excitatory postsynaptic potential which was followed by a large prolonged biphasic hyperpolarization. These signals were strikingly similar to those recorded in 1-month-old rats. In addition, large recurrent inhibitory postsynaptic potentials were produced by antidromic stimulation. By postnatal day 9 similar inhibitory postsynaptic potentials could be elicited in a majority of neurons of the CA1 subfield. As in mature pyramidal cells, application of GABA antagonists, such as bicuculline, selectively eliminated the antidromic inhibitory postsynaptic potential and the first component of the biphasic inhibitory postsynaptic potential generated by stimulation of stratum radiatum. In the CA3 subfield, this blockade of GABA receptors resulted in prolonged afterdischarges in slices from immature but not month-old rats. Measurements of the equilibrium potential and the conductance of antidromic inhibitory postsynaptic potentials in CA3 neurons were very similar when made during the first postnatal week and at 1 month of age. While on days 10-11 the equilibrium potential was very similar to measurements made at these other ages, the conductance was 3-4 times greater. The activity of glutamate decarboxylase, the synthetic enzyme for GABA, was very low at 3 days in hippocampus, and increased until 30 days of age at which time adult values were obtained. By comparison, hippocampal GABA levels were high early in postnatal life. Glutamate decarboxylase activities in microdissected CA3 and CA1 subfields were similar in immature hippocampus. These results demonstrate dramatic differences in the ontogenesis of functional GABAergic inhibitory synaptic transmission in the CA1 and CA3 subfields of rat hippocampus. The late development of GABA-mediated synaptic inhibition in the CA1 subfield could play a role in the susceptibility of immature hippocampus to seizures. However, the large GABA-mediated inhibitory postsynaptic potentials present in the CA3 subfield at the same age have a critical role in dampening neuronal excitability.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Postnatal development of GABA-mediated synaptic inhibition in rat hippocampus. 271 Mar 30

Subconvulsant doses (20 mg/kg) of pilocarpine administered to a kindled rat convert a kindled seizure to status epilepticus. The hippocampus is involved in such status epilepticus. Furthermore, evidence is accumulating that GABA-mediated inhibition in the hippocampus is chronically diminished by kindling. The studies presented here compared the electrophysiologic effects of pilocarpine in vivo in the CA1 region of the hippocampus in naive and amygdala-kindled rats. A paired pulse paradigm previously shown to quantify the potency of GABAergic inhibition was employed. Stimuli were delivered in the CA3 region of urethane-anesthetized rats and population spikes were recorded in the contralateral CA1 region. In naive rats, pilocarpine (6-60 mg/kg) caused a left shift in the input-output curve measuring stimulus intensity vs population spike amplitudes, indicating an increase in neuronal excitability. In addition, paired pulse inhibition was reduced for interpulse intervals less than 70 ms. In amygdala-kindled rats, neuronal excitability was also enhanced following pilocarpine administration. The potency of baseline paired pulse inhibition was decreased in kindled rats compared to naive controls. Following pilocarpine, inhibition for interpulse intervals less than 70 ms was further reduced, but to a lesser extent than in naive rats. These findings suggest that the ability of subconvulsive doses of pilocarpine to change a discrete kindled seizure triggered by one stimulus to status epilepticus depends on the suppression of GABAergic inhibition below a critical level.
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PMID:Reduction of paired pulse inhibition in the CA1 region of the hippocampus by pilocarpine in naive and in amygdala-kindled rats. 272 29


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