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

We recently described a pronounced neuronal loss in layer III of the entorhinal cortex (EC) in patients with intractable temporal lobe epilepsy (Du et al., 1993a). To explore the pathophysiology underlying this distinct neuropathology, we examined the EC in three established rat models of epilepsy using Nissl staining and parvalbumin immunohistochemistry. Adult male rats were either electrically stimulated in the ventral hippocampus for 90 min or injected with kainic acid or lithium/pilocarpine. Animals were observed for behavioral changes for up to 6 hr and were killed 24 hr or 4 weeks after the experimental treatments. At 24 hr, all animals that had exhibited a bout of acute status epilepticus showed a consistent pattern of neuronal loss in the EC in Nissl-stained sections. Neurodegeneration was most pronounced in layer III of the medial Ec at all dorsoventral levels. A few surviving neurons were frequently present in the lesioned area. An identical pattern of nerve cell loss was also seen in the EC of rats killed 4 weeks following the treatments. This lesion was completely prevented by an injection of diazepam and pentobarbital, given 1 hr after kainic acid administration. Immunohistochemistry demonstrated a relative resistance of parvalbumin-positive neurons in layer III of the medial EC. Taken together, these experiments indicate that prolonged seizures cause a preferential neuronal loss in layer III of the medial EC and that this lesion may be related to a pathological elevation of intracellular calcium ion concentrations.
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PMID:Preferential neuronal loss in layer III of the medial entorhinal cortex in rat models of temporal lobe epilepsy. 747 96

Gangliogliomas, dysembryoplastic neuroepithelial tumors (DNT) and glioneuronal malformations are frequently encountered in patients with pharmacoresistant focal epilepsies. In order to characterize the neurochemical profile of these neoplastic and malformative glioneuronal lesions, we have examined the presence of the alpha 1 subunit of the GABAA receptor, the N-methyl-D-aspartate receptor subunit 1 (NR1), glutamate decarboxylase, tyrosine hydroxylase, somatostatin, parvalbumin, and calretinin in 60 gangliogliomas, 11 DNT, 10 tuberous sclerosis-like lesions and 17 non-tuberous sclerosis-like glioneuronal malformations. All DNT and tuberous sclerosis-like lesions, 59 gangliogliomas (98%), and 13 non-tuberous sclerosis-like hamartias (76%) were positive for at least one of the markers. Despite a great variation between and within the different entities, the neurochemical profile was generally reminiscent of normal neocortex: glutamate decarboxylase, GABAA receptor and NR1 which are common in neocortical neurons were present in the great majority of the lesions and often showed high labeling indices. There were three tuberous sclerosis-like lesions (30%) that contained both NR1 and glutamate decarboxylase immunoreactive giant cells in addition to well-differentiated ganglion cells. This supports the idea that at least some of these giant cells are of neuronal origin. The oligodendroglia-like cells of DNT and glioneuronal hamartias did not show immunoreactivity for any of the markers. The very high incidence of ganglioglial lesions in patients with chronic focal epilepsies and the presence of neurotransmitter-producing enzymes, neurotransmitter receptors, neuropeptides, and calcium-binding proteins in many of these lesions suggests that they may play an active role in the pathogenesis of epileptic seizures.
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PMID:Neurochemical profile of glioneuronal lesions from patients with pharmacoresistant focal epilepsies. 766 58

Potential alterations in glutamate-utilizing excitatory circuits in resected human epileptogenic frontal and temporal neocortex were investigated by using immunocytochemical methods to visualize receptor subunits which comprise the AMPA/kainate (GluR2/3) and kainate (GluR5/6/7) receptor subtypes. Examination of the patterns of immunostaining in regions of neocortex that were identified as spiking and non-spiking based on intraoperative electrocorticography revealed dramatic, microzonal decreases in immunoreactivity for the receptor subunits examined. The patches of decreased immunostaining for GluR2/3 and for GluR5/6/7 were often coincident with respect to each other. However, such abnormal regions were not necessarily correlated with any particular electrocorticographically defined regions nor any overtly abnormal cytoarchitectural features in adjacent Nissl-stained sections. Moreover in many but not all cases, the focal regions of decreased receptor subunit immunoreactivity coincided with small patches of decreased parvalbumin immunoreactivity a calcium-binding protein which labels a subpopulation of powerful inhibitory GABAergic interneurons. These results indicate that in the human epileptogenic neocortex there may be alterations in particular excitatory and/or inhibitory synaptic systems at small, multiple neocortical foci, and that these alterations are found mostly in the same regions. We suggest that these alterations may contribute to the initiation and/or propagation of seizure activity.
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PMID:Microzonal decreases in the immunostaining for non-NMDA ionotropic excitatory amino acid receptor subunits GluR 2/3 and GluR 5/6/7 in the human epileptogenic neocortex. 782 Jun 13

Gerbils (Meriones unguiculatus) are known for their seizure sensitivity, which is dependent on an intact perforant path from the entorhinal cortex to the hippocampus. In contrast with other species, the perforant path in gerbils contains parvalbumin, a cytosolic high-affinity calcium-binding protein. Parvalbumin is known to be present in a subpopulation of GABA-containing neurons and is thought to be responsible for their physiological characteristics of fast spiking activity and lack of spike adaptation. Therefore, the question arose of whether this projection in gerbils is GABAergic or glutamatergic as in other species. In a first approach to this question, the effect of lesioning the origin of the perforant path, the entorhinal cortex, on levels of GABA and glutamate was determined by enzymatic-luminometric assay in single layers of the dentate gyrus of lyophilized brain sections. Parallel sections were cryofixed using an acidified acetone-formaldehyde mixture at -20 degrees C for 48 h, and subsequently stained for parvalbumin immunocytochemistry. Seven days after ablation of the entorhinal cortex, parvalbumin staining was undetectable in the termination zone of the perforant path, the outer two-thirds of the stratum moleculare. In parallel, glutamate content was reduced to 80% of controls (and of the unoperated contralateral side) but unchanged in the inner third of the stratum moleculare and in stratum granulare. GABA content was not significantly altered by the lesion. From these results, we conclude that in the gerbil as in other species, the perforant path contains glutamate.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Evidence for the colocalization of parvalbumin and glutamate, but not GABA, in the perforant path of the gerbil hippocampal formation: a combined immunocytochemical and microquantitative analysis. 790 49

Parvalbumin immunoreactivity is examined in the hippocampus of the Mongolian gerbil (Meriones unguiculatus) in controls and in animals subjected to 20 min of forebrain ischaemia produced by bilateral clipping of the carotids. In comparison with other species, the hippocampus of the gerbil is characterized by strong immunoreactivity of the (presumably excitatory) perforant pathway, and weak immunoreactivity (low numbers of neurons and scarce dendritic arbors) in nonpyramidal nerve cells (inhibitory neurons) of the CA1 area. These properties may play some role in the development and maintenance of seizures in this susceptible species. Parvalbumin immunoreactivity is rapidly and ephemerally increased in the hippocampus 15 min after reperfusion. Later on, there is a transitory decrease of parvalbumin immunoreactivity which is followed by an increase 6 h later in the stratum granulare hilus and CA3 area, and not until the first and second days in the CA1 area. This increase significantly surpasses the number of immunoreactive neurons in control animals in CA1 and CA3 from 48 h after reperfusion onwards. The effect is similar using different anaesthetics and does not occur in sham-operated animals. In contrast with these findings, the number of parvalbumin-immunoreactive neurons in the somatosensory cortex is not affected in our model of forebrain ischaemia. On the other hand, GABA-immunoreactive neurons in CA1 are preserved during the first week after reperfusion, although an increase in the number of these cells occurs at the end of this period. Delayed neuronal death occurs in the CA1 area 48 h after ischaemia, and marked reduction in the number of CA1 neurons is found by the end of the first week. Eighty per cent of the remaining cells in CA1 at day 7, and 83% at day 15, are parvalbumin-immunoreactive nonpyramidal neurons in contrast to 3% parvalbumin-immunoreactive cells in control animals. These findings indicate that GABAergic neurons in CA1 are preserved after forebrain ischaemia, and that parvalbumin in CA1 neurons is associated with survival.
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PMID:Parvalbumin immunoreactivity in the hippocampus of the gerbil after transient forebrain ischaemia: a qualitative and quantitative sequential study. 835 Sep 92

Neuroanatomical methods were used to determine if cocaine irreversibly injures neurons. Despite acute and chronic high-dose treatments for months that produced stereotyped behavior and seizures, and the use of a sensitive silver impregnation method, we were unable to find any evidence of neuronal damage anywhere in the brain. Since expression of the inducible 72 kDa heat shock protein (HSP72) is a sensitive indicator of potentially toxic neuronal stress, we next determined if cocaine evoked HSP72 expression. Even high doses of cocaine that evoked seizures did not induce HSP72 immunoreactivity anywhere within the brain, whereas kainic acid produced widespread HSP72 immunoreactivity and irreversible injury. Having failed to find indications of frank neurotoxicity, we examined peptide and protein cell marker immunoreactivities in search of cocaine-induced changes. Although cocaine treatment had no obvious effects on the patterns of hippocampal calbindin-D28K, somatostatin-, tyrosine hydroxylase- and parvalbumin immunoreactivities, cocaine reliably altered neuropeptide Y-like immunoreactivity (NPY-LI). Most notably, NPY-LI was expressed in hippocampal dentate granule cells and pyriform cortical neurons, which do not normally express it. Conversely, we noted decreased NPY-LI in dentate hilar neurons that normally do express it. Since both changes in NPY-LI were seen only in cocaine-treated rats that exhibited seizures, the role of seizure activity per se in producing the NPY changes was addressed in normal rats by electrical stimulation of the perforant path. Like cocaine, perforant path stimulation for as little as 15min evoked NPY-LI in granule cells but did not replicate the cocaine-induced decrease in hilar cell NPY-LI. These results suggest that cocaine does not irreversibly injure neurons in the rat, even at doses that induce seizures. However, cocaine produces long-lasting changes in NPY expression that are of unknown functional significance. Our inability to demonstrate cocaine-induced neuronal damage in rats should in no way be taken as evidence of its safety in humans.
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PMID:Cocaine neurotoxicity and altered neuropeptide Y immunoreactivity in the rat hippocampus; a silver degeneration and immunocytochemical study. 835 18

Mongolian gerbils (Meriones unguiculatus) are genetically predisposed to seizures, for which an involvement of hippocampal hyperexcitability and disinhibition has been suggested. The response in vitro of the hippocampal synaptic circuit upon exposure to an elevated extracellular calcium concentration is well known in the rat, and its dependence on inhibitory and excitatory transmission has been thoroughly studied. The purpose of the present investigation was to compare the influence of elevated extracellular calcium on inhibitory and excitatory transmission in the dentate area and the CA1 field of gerbil and rat hippocampal slices. Elevated calcium induced in the CA1 area of both animal species a long-term potentiation (LTP)-like response. Upon calcium exposure in the dentate area a decrease in population spike amplitude occurred in both gerbil and rat slices, indicating a similar degree of synaptic inhibition in the two species. However, in contrast to the effects known in the rat, elevated extracellular calcium failed to enhance the excitatory postsynaptic potential in the gerbil dentate area. This difference may depend on the species-specific, selective presence of the calcium-binding protein parvalbumin in perforant path terminals of the gerbil, which may be relevant to the susceptibility to seizures of this animal species.
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PMID:Absence of calcium-induced LTP-like response in the dentate area of seizure-prone gerbils and its relation to parvalbumin in the entorhinal perforant path synapse of this species. 838 16

In the gerbil (Meriones unguiculatus) hippocampal formation, the calcium-binding protein parvalbumin (PV) shows a unique species-specific distribution: it is present in the perforant path from the entorhinal cortex to the stratum molecular of the dentate are and cornu ammonis. A possible relation of this to the seizure-sensitivity of gerbils has been suggested. In addition, as in other species, PV is contained in a subpopulation of GABAergic nerve cells of the gerbil hippocampus. The characteristics of these PV-containing neurons are here described. Distribution and shape of the PV-positive neurons in general agreed with the features described for rat hippocampus with two notable exceptions: in CA2 PV-containing perikarya were densely crowded and gave rise to an intense immunoreactive plexus around the pyramidal cells and, in CA1, the number of stained neurons was variable, often much lower than in rats and occasionally not a single PV-positive neuron was present. In parasagittal brain sections of the lateralities 1.0, 1.6 and 2.2 mm from the midline, obtained from 27 male gerbils, the number of PV-containing neurons was determined. The data set obtained in CA3 and dentate area resembled unimodal distributions, while in CA1 a bimodal frequency distribution was present. Since parametric and non-parametric correlation tests rely on a unimodal distribution of the data set, they gave falsely significant values in CA1. The bimodal distribution suggests that, with respect to the PV-containing interneurons in CA1, two different populations of gerbils were included in our sample, those with many positive neurons and those with only a few. Since the nerve terminal staining is preserved also in those gerbils with only a few positive perikarya in CA1, it seems possible that an unknown factor influenced PV expression and storage in the soma. Sex, age, seasonal or circadian rhythm or quality of immunocytochemical staining did not influence the outcome of the quantitative analysis. However, a relation of the expression of the high affinity calcium buffering PV in interneurons and the individual seizure sensitivity of the gerbil is considered.
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PMID:Distribution of parvalbumin-containing interneurons in the hippocampus of the gerbil--a qualitative and quantitative statistical analysis. 856 51

Immunocytochemical methods were used to study alterations in inhibitory neuronal circuits in human neocortex resected during surgical treatment of intractable temporal epilepsy associated or not with brain tumours. The epileptogenic cortex was characterized and divided into spiking or non-spiking zones by intraoperative electrocorticography (ECOG). The resected cortex was cut into blocks, sectioned and stained immunocytochemically for visualization of glutamic acid decarboxylase (GAD), the calcium-binding protein, parvalbumin (PV) and glial fibrillary acidic protein (GFAP). A variety of alterations in cortical neuronal circuits as revealed by immunocytochemical and histological methods were found. Similar alterations in inhibitory neuronal circuits appear to occur independently of the primary epileptogenic site and pathology associated with epilepsy, which suggests that there is possibly a common basic underlying mechanism that leads to seizure activity. These changes were apparently unrelated to ECOG findings at surgery, which bring into question the value of the use of interictal epileptic discharges recorded by ECOG to guide cortical resections. The most conspicuous and common change was the loss of chandelier cells. The finding that these cells are among the most vulnerable types of GABAergic interneurons in the epileptogenic temporal cortex indicates that they might be of great functional importance, since the axon terminals of chandelier cells are likely to exert powerful regulation of impulse generation in cortical pyramidal cells. Therefore, these cells might represent a key component in the aetiology of human epilepsy.
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PMID:Inhibitory neurons in the human epileptogenic temporal neocortex. An immunocytochemical study. 881 95

1. Naturally occurring inherited epilepsy is common among Mongolian gerbils, providing an opportunity to identify neurological factors that correlate with seizure behavior. In the present study we examine the ontogeny of seizure behavior and compare the electrophysiology and anatomy of the dentate gyrus in epileptic and nonepileptic gerbils. 2. Behavioral seizure testing revealed that young gerbils do not begin having seizures until they are 2 mo of age, at which time seizure incidence across animals is at its highest level. Most seizure-positive juvenile gerbils became epileptic adults, but 30% outgrew their epileptic condition. 3. The number of somatostatin- and parvalbumin-immunoreactive neurons in the dentate gyrus and Ammon's horn was counted, with the use of quantitative stereological techniques, in juvenile and adult gerbils. No significant differences were detected between epileptic and nonepileptic groups. 4. In dentate gyrus field potential responses to perforant path stimulation, adult epileptic gerbils showed enhanced paired-pulse inhibition at short (30 ms) interstimulus intervals and enhanced facilitation at intermediate (70 ms) intervals compared with nonepileptic controls. These differences were most pronounced when stimuli were delivered at faster (1.0 Hz) rather than slower (0.1 Hz) rates. 5. Compared with seizure-negative juveniles, seizure-positive juveniles showed the same pattern of paired-pulse response abnormalities as epileptic adults. However, seizure-positive juveniles had a lower threshold for maximal dentate activation than epileptic adults. 6. These results demonstrate similar functional abnormalities in the dentate gyri of epileptic adult gerbils and in juvenile gerbils before they experience multiple seizures. Such findings suggest that abnormalities in functional inhibition of the dentate gyrus network precede and therefore might contribute to overt seizure activity.
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PMID:Electrophysiological correlates of seizure sensitivity in the dentate gyrus of epileptic juvenile and adult gerbils. 889 92


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