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

C57BL/10Bg sps/sps mice display behavioral arrest, similar to generalized absence seizures. Compared with the parent strain C57BL/10Bg SPS/SPS, the activities of glutamate decarboxylase (GAD, E. C. 2.6.1.15), GABA aminotransferase (GABA-T, E. C. 2.6.1.19), aspartate aminotransferase (ASP-T, E. C. 2.6.1.1), and glutamate dehydrogenase (GDH, E. C. 1.4.1.3) in whole brain crude supernatant were significantly reduced in the sps/sps mice. Alanine aminotransferase activity (ALA-T, E. C. 2.6.1.2), was not altered in any of the strains, and normalization of GAD, GABA-T and GDH activities by that of ALA-T, further revealed significant differences between the normal strain (SPS/SPS), the heterozygotes (SPS/sps), and behavioral arrest (sps/sps) mice. These results suggest the possible involvement of GABAergic and glutamatergic neurotransmission in the absence-like behavior displayed by sps/sps mice. Open field behavior of C57BL/10Bg sps/sps mice is characterized by periods of marked inactivity which easily distinguish affected homozygotes, from their heterozygotes littermates.
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PMID:The C57BL/10Bg sps/sps mouse: a mutant with absence-like seizures; neurochemical and behavioral correlates. 239 34

It is well known that a dietary restriction of vitamin B-6 during gestation and lactation produces spontaneous seizures in neonatal animals. Since pyridoxal phosphate, one of the biologically active forms of vitamin B-6, is the cofactor for GAD the neonatal seizures have been attributed to low levels of brain GABA as a result of cofactor depletion. Although GABA levels are significantly lower in B-6 restricted neonatal rats with spontaneous seizures, seizure activity is not present in B-6 deficient adult rats or 28 day old rats in the present study, despite significantly low levels of brain GABA. These facts suggest that depletion of GABA is not the only biochemical alteration essential for the emergence of seizures. In the present study, the effect of vitamin B-6 undernutrition on the concentrations of the neuroactive amino acids, Glu, Gly, Tau, and GABA was determined in selected regions of the developing rat brain. The results show that the concentrations of Glu, Tau, and GABA were significantly lower and GLY significantly higher in selected brain regions of the B-6 restricted 14 day old rat compared to control tissue. Most of these changes were unique to 14 days of age, the time when spontaneous seizures are observed, and not present at 28 or 56 days of age when seizures are absent. This pattern of amino acid changes in the brain and the magnitude of the changes was consistent with those measured in a variety of chemically-induced animal models of epilepsy and in human epileptic foci.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Regional changes in the concentrations of glutamate, glycine, taurine, and GABA in the vitamin B-6 deficient developing rat brain: association with neonatal seizures. 257 23

In order to study the extent of inhibition in human epileptic hippocampus, we recorded extracellular unit activities of human hippocampal neurons and their responses to single pulse stimulation in temporal lobe epilepsy patients during interictal periods. The criteria for diagnosing the hippocampus as epileptic were: (1) all seizures originated in that one hippocampus, (2) surgical removal of that hippocampus resulted in seizure relief, and (3) the surgically excised hippocampus was sclerotic. Analysis of firing pattern by cross-correlation showed that synchronized firing between neurons occurred only in the epileptic hippocampus. However, synchronized firing was not limited to only bursting neurons, as previously reported in some animal models of epilepsy, but was also observed among non-bursting neurons in the epileptic hippocampus. Furthermore, no significant difference in distribution of burst-discharge neurons was found between epileptic and non-epileptic hippocampi. In response to single pulse stimulation, neurons in both 'normal' (contralateral hippocampus) and epileptic hippocampus showed a rapid increase of firing (excitation), cessation of firing (inhibition), or a sequence of both (initial excitation followed by inhibition). However, a significant difference was found in the duration of the inhibition between synchronously firing neurons and non-synchronously firing neurons: the inhibition evoked by a single stimulation in synchronously firing epileptic neurons was significantly longer (373.8 msec +/- 35.9 S.E.M., P less than 0.005) than that of non-synchronously firing neurons (83.9 msec +/- 8.9 S.E.M.). Moreover, prolonged inhibition in synchronously firing epileptic neurons could occur with little or no prior excitation, suggesting that this inhibition does not necessarily depend on an intrinsic Ca2+-dependent K+-mediated after-burst hyperpolarization but is rather likely to be synaptic. As this inhibition was longer when epileptic neurons fired in synchrony, it could be interpreted that principal neurons recruited more recurrent inhibitory circuits by firing synchronously. By taking into account the previously reported neurophysiological evidence in human in vitro epileptic tissue showing GABA-mediated inhibition and the neuroanatomical evidence in excised human epileptic hippocampus showing GAD-positive neurons and synapses, our data suggest that, in human chronic epileptic hippocampus, recurrent inhibition remains functional, and alterations in GABA-mediated inhibition may not represent the critical change responsible for seizure generation.
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PMID:Inhibition in synchronously firing human hippocampal neurons. 273 21

The present study was designed to test the hypothesis that chronic gamma-aminobutyric acid (GABA) disinhibition of granule cells could explain permanent kindled epileptogenicity. Quantitative and statistical comparisons of glutamate decarboxylase immunoreactivity (GAD-IR), the synthesizing enzyme for GABA, were made of GAD-IR cells and puncta in stratum granulosum of the fascia dentata. The use of GAD immunocytochemistry in kindled and control tissue was used to allow direct anatomic confirmation that we were measuring changes in GAD-IR which would represent GABA synthesis for release by the recurrent inhibitory system of the fascia dentata. Immediately after the last kindled seizure, optically detected GAD-IR puncta densities were significantly reduced in stratum granulosum. At 3 or 7 days after the last kindled seizure, GAD-IR was normal in puncta, indicating that the transient GAD-IR loss was probably a metabolic response to the recent seizure represented by over-use of GAD needed for synthesis of GABA after a prolonged kindled seizure. When the prolonged kindled seizures were discontinued GAD-IR recovered in the puncta. This transient effect did not occur in other areas such as Ammon's horn (CA3) or substantia nigra. The extent of the GAD-IR loss showed no correlation with the severity of the final behavioral seizure (R = 0.23), or the final afterdischarge (AD) duration in entorhinal cortex (R = 0.17) or motor cortex (R = 0.53). A massed stimulation control group given 19 shorter-duration ADs every 10 min (non-kindling) did not reduce GAD-IR. These findings support the hypothetical model that prolonged kindled seizures release excessive GABA which depletes GAD in axon terminals for 1 day after the seizure. However, such a transient suppression of GAD-IR provides no evidence that disinhibition contributes to the kindling process, because kindling proceeds normally with inter-seizure intervals as long as 1 week. The finding of full recovery of GAD-IR within 1 week does not support the model of loss of GABA inhibition to explain the permanency of kindled epileptogenesis.
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PMID:Recovery of decreased glutamate decarboxylase immunoreactivity after rat hippocampal kindling. 291 45

Several previous studies have suggested a strong GABA-mimetic action of the endogenous brain imino acid, L-pipecolic acid (L-PA). In the present study, these observations were evaluated using electrophysiological and neurochemical methods. In contrast to published data our electrophysiological studies on rat cortical neurones in situ showed only a weak, but bicuculline-sensitive depressant action of L-PA on cortical neurones. Furthermore, L-PA proved to have no affinity for any of the three components of the GABA-benzodiazepine-chloride channel receptor complex. However, using a modification of published methods a weak affinity for the GABA-B receptor site was demonstrated (IC50 = 1.8 X 10(-3) M). L-PA showed no anticonvulsive activity in several tests; in particular, it did not protect mice from seizures induced by inhibition of L-glutamate-1-decarboxylase (EC 4.1.1.15: GAD). L-PA had a very weak action on brain GABA levels of mice, and did not modify the rate of GABA synthesis. In conclusion, these results are not compatible with a strong in vivo interaction between L-PA and GABA-mediated inhibitory transmission.
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PMID:Dose pipecolic acid interact with the central GABA-ergic system? 302 50

Various populations of mice exhibit differential sensitivity to seizure-inducing agents. The relationship of seizure susceptibility to alterations in the GABA receptor complex was investigated in six different populations of mice consisting of four inbred strains (C57BL, DBA, C3H, and BALB) and two selected lines (long sleep and short sleep). Seizure activity was induced by intraperitoneal administration of the GAD inhibitor, 3-mercaptopropionic acid, and latencies to seizure onset and tonus were measured. In naive mice of the same populations, GABA enhancement of 3H-flunitrazepam binding was measured in extensively washed whole brain membranes at several GABA concentrations. Both differential seizure sensitivity to 3-mercaptopropionic acid and differential enhancement of 3H-flunitrazepam binding by GABA were observed in these six populations of mice. Correlational analyses indicated a positive correlation between the degree of GABA enhancement of 3H-flunitrazepam binding and resistance to the seizure-inducing properties of 3-mercaptopropionic acid. These data suggest that genetic differences in sensitivity to seizure-inducing agents that disrupt the GABAergic system may be related to differences in coupling between the various receptors associated with the GABA receptor complex.
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PMID:Correlation between the enhancement of flunitrazepam binding by GABA and seizure susceptibility in mice. 303 5

Spontaneous clonic-tonic seizures were occasionally observed in inbred AE mice of both sexes. Determination of seizure thresholds in this strain showed that both female and male AE mice had electroconvulsive thresholds that were markedly lower than those of other strains of mice, whereas susceptibility to seizures induced by pentylenetetrazol was not increased. The antiepileptic drug phenobarbital was much less effective in blocking electroconvulsions in AE mice than in other strains. Similarly, valproic acid was less effective in protecting against pentylenetetrazol-induced seizures. These differences in anticonvulsant efficacy could be explained only partly by differences in pharmacokinetics, thus indicating a lower responsiveness of AE mice to antiepileptic drugs. Determination of the GABA-synthesizing enzyme glutamic decarboxylase in different brain regions showed no significant difference between AE mice and normal NMRI mice except for a lower GAD activity in corpus striatum of male AE mice. The data indicate that AE mice may be an interesting new genetic model of epilepsy.
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PMID:AE mice: an inbred mouse strain with interesting features for epilepsy research. 309 6

Partial complex seizures are known to arise from abnormal firing of neurons in cortex that has histologic abnormalities associated with tumors, infarcts, or neuron loss. The latter pathology of sclerosis is most frequently found in the hippocampus, and partial seizures from this region are focalized by direct electrical recordings and treated by anterior temporal lobectomy. Although we can link this hippocampal sclerosis to nearby hyperexcitability, the synaptic mechanisms involved in hippocampal seizure genesis are not yet known. We have used in vivo microelectrode recordings from hippocampal neurons and found rare instances of anomalous bursting patterns as well as coupled firing. Postinhibitory "rebound excitation" has also been recorded, supporting the concept that synchronized hippocampal outputs are important for seizure genesis. Immunocytochemistry of GAD-positive inhibitory interneurons indicates no significant loss in inhibition in the sclerotic hippocampus and a normal number of inhibitory interneurons in its output target, the presubiculum. The presubiculum, with its multi-layered cortex, may amplify and propagate seizures to other cortices. Golgi and electron microscopy of epileptic neurons have shown pre- and postsynaptic alterations that may contribute to seizure genesis. Finally, ultrastructural analysis of capillaries in sclerotic hippocampus indicates deficient plasma-tissue transport that may contribute to cell loss or may alter neuronal excitability.
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PMID:Neuronal, dendritic, and vascular profiles of human temporal lobe epilepsy correlated with cellular physiology in vivo. 370 28

The number of GABAergic neurons as determined by GAD immunocytochemistry and total neurons as determined from Nissl preparations were counted and classified at the light microscopic level in the inferior colliculus (IC) of the genetically epilepsy prone rat (GEPR) and the non-epileptic Sprague-Dawley (SD) strain of rat. GAD-positive neurons are abundant in the IC and a significant increase in the number of GAD-positive neurons occurs in the GEPR as compared to the SD in all three subdivisions. However, the most pronounced difference occurs in the ventral lateral portion of the central nucleus, where there is a selective increase in the small (200%) and medium-sized (90%) GABAergic somata (10-15 microns in diameter and 15-25 microns in diameter, respectively). As determined from Nissl preparations an increase in total numbers of neurons also occurs. Thus, a 100% increase in the number of small neurons and a 30% increase in the number of medium-sized neurons occur in the adult GEPR as compared to the SD rat. A statistically significant increase in the numbers of small neurons also occurred in the IC of the young GEPR. At 4 days of age, a 55% increase in the number of small neurons was found, and at 10 days of age this increase was 105%. The numbers of the medium and large neurons were similar in the older group of rats. These data suggest that the increase in cell number observed in the adult GEPR is not compensatory to the seizure activity, but may either be genetically programmed or be a failure of cell death. Based on other studies of genetic models of epilepsy, we propose that the additional GABAergic neurons may disinhibit excitatory projection neurons in the IC.
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PMID:Anatomical changes of the GABAergic system in the inferior colliculus of the genetically epilepsy-prone rat. 374 30

Our current understanding of focal seizures strongly suggests a model of damage and associated synaptic reorganization that leads to periodic 'spontaneous' hyperexcitation and/or sustained firing that generates seizures. Our working model of a human epileptic focus assumes that there will often be inexcitability near the damage (hippocampus proper); however, the anomalous circuitry will occasionally lead to hyperexcitability whenever these anomalous (epileptic) circuits are activated synchronously in sufficient numbers to propagate discharges to normal tissue (e.g., the presubiculum) which would be normally excitable. The key role of rebound excitation following prolonged inhibition in the hippocampus is strongly supported by both physiologic and GAD immunologic results. Our ability to directly test the level of excitability of hippocampal and presubicular neurons in vivo, followed by microanatomical studies of the same resected tissue, will allow us to test our model and revise it as our results become more complete. Also, our findings will be important for relating synaptic mechanisms of seizure genesis to those demonstrated in various experimental models of focal hippocampal seizures.
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PMID:Metabolic, morphologic and electrophysiologic profiles of human temporal lobe foci: an attempt at correlation. 378


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