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Query: UMLS:C0014547 (focal epilepsy)
 1,627 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

It was discovered in 1966 that the senegalese baboon (Papio papio) exhibits a photosensitive epilepsy. This finding has led, among other work, to the neurophysiological study of this epilepsy. Although in some characteristics the baboon's photosensitive epilepsy differs from that of man, it can be considered that this animal presents a real model of essential epilepsy, for the study of the human disease. 2. In the baboon, the EEG disturbances triggered by intermittent light stimulation at 25 Hz appear first at the level of the frontal cortex (area 6). At this level, recordings of single unit discharges show an activation of cortical neurones similar to that observed in human patients with focal epileptic lesions ; at the occipital level, the only modification observed is a change in the resting membrane potentials, in the direction of disinhibition. 3. The analysis of cortical visual evoked responses demonstrated the presence of short latency visual afferents at the frontal cortex level, as well as a high level of hyperexcitability for the visual modality. The most photosensitive animals can be distinguished by a more marked frontal hyperexcitability and by slight differences in the form of both the occipital evoked responses (decrease in amplitude of the early part of the response, frequent absence of wave IV) and the frontal ones (higher amplitude of the later part of the responses). In some of the animals, whether they were photosensitive or not, we found high amplitude frontal visual evoked responses resembling spikes and waves. 4. Certain observations in both man and the photosensitive baboon suggested the possible involvement of periocular somatic afferents in the triggering of paroxysmal manifestations. The study of these cortical projections in the baboon showed that they possess certain specific characteristics which distinguish them from the other somatic projections (short latency, large frontal spread and ipsilateral responses of higher amplitude than contralateral). It seems, however, that if they play a role in the epileptic manifestations, these periocular projections are not required to trigger this behaviour. 5. The baboon frontal lobes seem therefore to be an area receiving multimodal projections, possessing a particular sensitivity to visual afferents, and functionally equivalent to a zone of focal epilepsy as might be met with in man or animals. 6. The results are discussed in the light of observations made on the same or other species, or on other types of epilepsy. In particular, the totality of the visual afferents arriving at the occipital level appears to be necessary to trigger epileptic manifestations. Finally, these results present several arguments in favour of the cortical theory of generalised epilepsies, as well as substantiating the value of the baboon as an animal model for photosensitive epilepsy in man.
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PMID:[Frontal cerebral cortex and photic epilepsy of the baboon Papio papio (author transl)]. 81 47

The contemporary neuroanatomist has a number of available methods to analyze epileptic brain tissue. Many studies have utilized Nissl- and Golgi-stained preparations to determine that gliosis and neuronal loss occur at epileptic foci as well as a decrease in the dendritic spine density. These structural changes did not reveal any specific basic mechanism that may cause epileptic activity. In contrast, the relatively newer techniques in neurocytology provide functional data that relate to the physiology and chemistry of the brain tissue. The use of immunocytochemical, histochemical, and receptor ligand-binding autoradiographic methods have aided in the understanding of cellular neurochemistry in both normal and epileptic tissue. In addition, the use of intracellular horseradish peroxidase and recording and quantitative morphological methods at both light- and electron-microscopic levels has helped gain insights into the functional state of synapses and neurons. Together, these methods have been utilized to help unravel the mystery of epilepsy. Our laboratory has utilized immunocytochemical and quantitative light- and electron-microscopic methods to analyze four models of epilepsy; two resemble posttraumatic focal epilepsy, and the other two are genetic models of epilepsy. Our data indicate that a preferential loss of cortical GABAergic, inhibitory terminals occurs at posttraumatic epileptic foci. In contrast, the genetic models of epilepsy did not display a loss of GABAergic terminals. Instead, specific brain regions of epileptic animals had an increased number of GABAergic neurons and terminals. These data indicate that two different neuronal circuits may provide the anatomical substrate for epileptic activity: loss of inhibition and disinhibition.
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PMID:Contemporary methods in neurocytology and their application to the study of epilepsy. 308 36

The brains of seizure-sensitive (SS) and seizure-resistant (SR) gerbils were studied with an immunocytochemical method to localize glutamic acid decarboxylase (GAD) to determine whether a defect existed in the inhibitory GABAergic system similar to that which has been reported in animal models of focal epilepsy in which GABAergic cell bodies and terminals are decreased in number. A major difference between the two strains of gerbils was found in the number of GABAergic neurons in the hippocampal formation. Specifically, a paradoxical increase occurred in the number of glutamate decarboxylase GAD-immunoreactive neurons: there were approximately 65% more GABAergic cells within the dentate gyrus and the CA3 region of the hippocampus in the SS gerbils. Furthermore, the density of GAD-immunoreactive puncta, the light microscopic correlates of synaptic boutons, was greater in the SS animals. Other histological methods were used to determine if the difference between SS and SR gerbils was specific for the GABAergic system. Nissl-stained preparations showed that the number of granule cells in the dentate gyrus was 20% greater in SS gerbils than in SR gerbils. An examination of some hippocampal afferents, efferents, and intrinsic connections with acetylcholinesterase histochemistry and the Timm's stain for heavy metals demonstrated no differences between the two strains. In addition, Golgi-stained preparations of the dentate gyrus indicated that the morphology of basket cells did not differ between the two strains nor between the gerbil and the rat. Several brain regions in addition to the hippocampus were studied to determine whether or not the increased number of GAD-immunoreactive neurons was specific for the hippocampal formation. These regions included the substantia nigra, motor cortex, and nucleus reticularis thalami and were selected because they contain large populations of GABAergic neurons and have been implicated in seizure activity. No differences between the two strains were detected in any of these regions. Therefore, a major morphological difference between the brains of SS and SR gerbils exists in the hippocampal formation of SS gerbils in which an increase occurs in the number of GABAergic neurons and granule cells. If these additional inhibitory neurons act mainly to inhibit other inhibitory neurons, the net effect would be increased disinhibition of the principal excitatory neurons of the hippocampal formation. This could lead to seizure activity within the hippocampal formation and at distant sites through multiple synaptic connections.
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PMID:Hippocampus of the seizure-sensitive gerbil is a specific site for anatomical changes in the GABAergic system. 361 18

Disinhibition syndromes, ranging from mildly inappropriate social behavior to full blown mania, may result from lesions to specific brain areas. Several studies in patients with closed head injuries, brain tumors, stroke lesions, and focal epilepsy have demonstrated a significant association between disinhibition syndromes and dysfunction of orbitofrontal and basotemporal cortices of the right hemisphere. Based on the phylogenetic origin of these cortical areas and their main connections with dorsal regions related to visuospatial functions, somatosensation, and spatial memory, the orbitofrontal and basotemporal cortices may selectively inhibit or release motor, instinctive, affective, and intellectual behaviors elaborated in the dorsal cortex. Thus, dysfunction of these heteromodal ventral brain areas may result in disinhibited behaviors.
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PMID:Mechanism of disinhibition after brain lesions. 904 3

It has been hypothesized that a disruption of gamma-aminobutyric acid (GABA) receptor-mediated processes may be involved in the pathophysiology of focal epilepsy. This disinhibition hypothesis has been postulated from the results of in vitro experiments of the interictal activity of focal epilepsy. Less is known, however, about how disinhibition may be involved in the production of the ictal activity. We therefore examined the pharmacological effects of selective agonists and antagonists of GABA(A) and GABA(B) receptors on ictal-like afterdischarges (ADs) induced following repetitive high-frequency electrical stimulation in the CA1 region of rat hippocampal slices. The GABA(A) receptor antagonist bicuculline (5 microM) fully blocked AD generation, as did the GABA(A) receptor agonist muscimol (2 microM), which is thought to produce a tonic inhibition during application. However, the benzodiazepine receptor agonist diazepam (5 microM), which enhances the inhibitory postsynaptic potential induced by synaptically released GABA, increased the number of spikes in the AD to 148.3% of the control value. On the other hand, the GABA(B) receptor antagonist phaclofen (1 mM) increased the number of spikes in the AD to 234.7% of the control value, while the GABA(B) receptor agonist baclofen (5 microM) reduced it to 46.9%. We therefore conclude that synaptic, but not tonic, activation of GABA(A) receptors appears to be necessary for ictal-like AD generation, while GABA(B) receptor activation plays a protective role. We therefore propose a modification to the simple disinhibition hypothesis.
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PMID:Involvement of GABA(A) and GABA(B) receptors in afterdischarge generation in rat hippocampal slices. 1082 20