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Showing papers on "Epileptogenesis published in 1985"


Journal ArticleDOI
01 Oct 1985-Nature
TL;DR: It is reported that manipulations of excitatory amino acid transmission and cholinergic transmission can also elicit seizures from this site, and this region is therefore a site of action for the epileptogenic effects of neuroactive agents with diverse mechanisms of action.
Abstract: Antagonists of gamma-aminobutyric acid (GABA)- or glycine-mediated neurotransmission, muscarinic cholinergic agonists, and excitatory amino acids and their analogues are all considered to be potent chemoconvulsant agents. However, although systemic injections of these agents have been used to create experimental models of generalized epilepsy, there has been no identification of a specific locus at which any of these drugs act to initiate generalized seizures. We recently located a forebrain region from which seizures can be elicited by the GABA antagonist bicuculline, and now report that manipulations of excitatory amino acid transmission and cholinergic transmission can also elicit seizures from this site. Bilateral clonic seizures can be elicited after unilateral application of picomole amounts of bicuculline, kainic acid or carbachol and micromole amounts of glutamate. Local application of the GABA agonist muscimol prevents the appearance of seizures on subsequent microinjection of all convulsant agents examined, whereas local application of the muscarinic antagonist, atropine, only prevents seizures induced by carbachol. This region is therefore a site of action for the epileptogenic effects of neuroactive agents with diverse mechanisms of action; it may also represent a site at which GABA agonists could function therapeutically to control epileptogenesis.

388 citations


Journal ArticleDOI
TL;DR: It was possible to demonstrate, in humans, the three stages of secondary epileptogenesis previously documented in animals, and a pharmacologic test is described that separates the reversible from the irreversible stage of secondary epilepsy and allows prediction of the results of surgical removal of the primary focus.
Abstract: • It is difficult to prove the existence of secondary epileptogenesis in man. In the majority of cases of human focal epilepsy, where the cause is likely to be trauma, infection, or vascular disease, the occurrence of additional or new epileptogenic foci is usually attributed to multiple primary injuries (maturing at different rates), or to progressive disease. Cerebral tumor is the only common cause in which the probability of multiple primary lesions is vanishingly low. Therefore, a personally followed series of cases of cerebral tumor seen as epilepsy are reviewed in which clinical, electrophysiologic, and pharmacologic data are analyzed for evidence of secondary epileptogenesis. Such evidence was found in 34% of our tumor patients. It was possible to demonstrate, in humans, the three stages of secondary epileptogenesis previously documented in animals. A pharmacologic test is described that separates the reversible from the irreversible stage of secondary epileptogenesis and allows prediction of the results of surgical removal of the primary focus.

313 citations


Journal ArticleDOI
TL;DR: Kainic acid lesions of hippocampal subfields CA3-CA4 produced dramatic synchronous afterdischarge activity in subfield CA1 when studied 2-4 weeks post-lesion in the in vitro slice preparation.

98 citations


Journal ArticleDOI
TL;DR: A marked enhancement in extracellular calcium changes, induced by electrical stimulation or by iontophoresis of excitatory aminoacids was found in kindled tissue, implying that changes in dendritic calcium conductances are involved in kindling epileptogenesis.
Abstract: Daily repeated tetanic electrical stimulation (kindling) of the brain may cause a long term enhancement of synaptic transmission and epileptiform activity of progressive severity and generalisation, eventually leading to spontaneous seizures. Evidence for a cellular mechanism underlying kindling has been obtained in vitro in slices from the hippocampus of kindled rats. A marked enhancement in extracellular calcium changes, induced by electrical stimulation or by iontophoresis of excitatory aminoacids was found in kindled tissue. This implies that changes in dendritic calcium conductances are involved in kindling epileptogenesis.

88 citations


Journal ArticleDOI
TL;DR: The key elements in the development of epileptogenesis appear to be the capacity of membranes in some (pacemaker) neurons to develop intrinsic burst discharges, the presence of disinhibition, and the proper excitatory synaptic circuitry.
Abstract: The key elements in the development of epileptogenesis appear to be the capacity of membranes in some (pacemaker) neurons to develop intrinsic burst discharges, the presence of disinhibition, and the proper excitatory synaptic circuitry. It is likely that the relative role of each of these processes will differ at different sites in the central nervous system which are prone to epileptogenesis. Synchronization of neuronal populations is a vital element in the development of focal discharge and a variety of mechanisms, including those dependent upon excitatory postsynaptic potentials, and other interactions are possible. Pathological processes may alter some or all of these regulatory mechanisms. However, different pathological entities presumably produce epileptogenesis through different combinations of pathogenetic mechanisms.

73 citations


Book ChapterDOI
01 Jan 1985
TL;DR: Development of the centrencephalic concept in the study of epilepsy was guided by extensive electrographic and clinical observations by the Montreal school, which excelled in excising the focal cortical area of epileptogenesis.
Abstract: Development of the centrencephalic concept in the study of epilepsy was guided by extensive electrographic and clinical observations by the Montreal school, which excelled in excising the focal cortical area of epileptogenesis (Penfield and Jasper, 1954). This theory attempted to explain generalized seizures by postulating that an epileptogenic “focus” existed in a hypothetical network of neurons in the higher brainstem near the midline, having equal and close to-and-fro interconnections with widespread cerebral cortical areas of both hemispheres by virtue of its central location. Penfield and Jasper were careful to state that they did not envisage the “centrencephalon” in anatomical terms and they emphasized further the importance of cortico-subcortico-cortical interaction for electroclinical manifestations of generalized seizures. This theory was convenient and useful in explaining generalized 3/sec spike and wave discharges as well as for explaining the secondary bilateral synchrony frequently resulting from lateralized pathophysiology.

37 citations


Journal ArticleDOI
TL;DR: The findings underscore the necessity of the conceptual differentiation between the EEG mirror focus and the epileptogenic focus capable of generating clinical seizures and the importance of dissecting interictal behavior reflecting a “continuous disorder of neuronal function,” which may cause symptoms other than seizures.
Abstract: Despite ready bilateralization of ictal and interictal EEG discharge throughout cortical kindling, the rate of convulsive seizure development was slow at both orbital and mesial frontal sites, even in the epileptic baboon. However, convulsive generalization occurred swiftly from the mesial frontal cortical (MF) sites once conjugate head, eye, and body adversion developed in the three primate species examined. Only epileptic baboons developed Stage 5 bisymmetrical and bisynchronous convulsion. Stimulation of the contralateral homotopic mesial cortical site readily produced afterdischarge that remained localized and convulsive seizure development did not occur. The findings suggest that (a) the frontal lobe plays an important role in the generation of nonconvulsive seizures, (b) the frontorolandic cortex plays a unique role in convulsive seizure generalization, (c) the role of the intrinsic (genetic) factor is significant in determining the quality of the kindled seizure, and (d) the development of focal epileptogenesis at one MF site interferes with clinical seizure development at the "mirror focus." Our findings underscore (a) the necessity of the conceptual differentiation between the EEG mirror focus and the epileptogenic focus capable of generating clinical seizures and (b) the importance of dissecting interictal behavior reflecting a "continuous disorder of neuronal function," which may cause symptoms other than seizures.

26 citations


Journal ArticleDOI
TL;DR: Adult offsprings of rats treated with daily injection of chlordiazepoxide during pregnancy showed a significant decrease in benzodiazepine receptors in the cortex and the cerebellum without apparent changes in receptor affinity, and a reduced susceptibility to metrazol-induced epileptogenesis paralleled this change.

24 citations


Book ChapterDOI
01 Jan 1985
TL;DR: This chapter will focus upon the role of the corpus callosum in secondary epileptogenesis, the process by means of which an initially normal neural network, as a consequence of its chronic exposure to the activity of a primary (1°) epileptic lesion, develops epileptogenic properties of its own.
Abstract: This chapter will focus upon the role of the corpus callosum in secondary epileptogenesis. Secondary (2°) epileptogenesis may be defined as the sum total of that series of events by means of which an initially normal neural network, as a consequence of its chronic exposure to the activity of a primary (1°) epileptic lesion, develops epileptogenic properties of its own. This transformation of the satellite or target network involves passage through several stages of development, as will be described on pp. 17 and 18 below. The primary epileptic lesion may be produced by any of a wide variety of locally acting metals or drugs [see Purpura et al. (1972) for details] or by chronic, recurrent electrical stimulation (kindling), or may arise as a consequence of some injury, as in the naturally occurring epilepsies in man. No matter what the causative agent of the primary lesion, there is a substantial likelihood that the latter will ultimately give rise to satellite foci in distant, but synaptically related, cerebral regions. These secondary foci eventually develop all the properties of the primary focus, including that of giving rise to clinical seizures, of establishing their own secondaries (tertiary epileptogenesis) and of maintaining the newly acquired epileptogenic behavior even after removal of the orginal or 1° focus. The process therefore represents a true spread of epileptogenicity to originally uninvolved regions of the brain. It is a kind of spread, however, that must be sharply distinguished from that which occurs when a formerly quiescent focus begins to spread into surrounding normal tissue and to give rise to clinical convulsive behavior.

10 citations


Journal ArticleDOI
TL;DR: It is suggested that there may be a laminar segregation of neocortical inhibition, possibly glycine-mediated in layers 2-3 and probably gamma aminobutyric acid (GABA)-mediated in layer 4, which has been shown to be most susceptible to epileptogenic effects of penicillin and bicuculline.

9 citations


Journal ArticleDOI
TL;DR: It is suggested that, although lead intoxication starting in neonatal life does not appear to affect the susceptibility to development of amygdaloid kindled seizures, it may enhance seizure severity in this model of epileptogenesis.

Book ChapterDOI
01 Jan 1985
TL;DR: The in vivo model of kindling with the in vitro method of hippocampal slices and in vitro technique enabled us to record accurately, in tissue obtained from kindled rats, the laminar profiles of changes in extracllular potassium [K+]O and extracellular calcium [Ca2+)O induced by different methods.
Abstract: Daily repeated tetanic stimulation of mild physiological intensity leads, in many parts of the brain, to the gradual development of an epileptogenic focus. This treatment (kindling) may finally even result in generalized tonic clonic convulsions. Since its first description in 1969 by Goddard [7], this experimental model of epilepsy has drawn considerable attention as one of the few models of permanent plasticity in the adult vertebrate brain. Much work has been devoted to defining optimal parameters for stimulation, to determine the sensitivity for kindling of different regions of the brain in a variety of species, and to exclude the phenomenon from being an implantation artifact (reviews are given by Racine [29] and McNamara et al. [20]. Despite the fact that a lot of knowledge has been acquired in this way, still little is known about the cellular mechanisms that underlie kindling epilepsy. Changes in polarity of epileptiform transients recorded in vivo during kindling epileptogenesis suggested that some dendritic process might be involved [16, 32]. Furthermore, it is known from several other models of epilepsy that variations in the concentrations of calcium and potassium in the extracellular space play an important role in the stability of neuronal circuits and that the concentrations of these ions can vary considerably during epileptiform activity [10,13, 23, 24–26, 31, 33]. In order to investigate the underlying mechanisms of kindling in more detail at a cellular level, we combined the in vivo model of kindling with the in vitro method of hippocampal slices [3,11,18]. The in vitro technique enabled us to record accurately, in tissue obtained from kindled rats, the laminar profiles of changes in extracellular potassium [K+]O and extracellular calcium [Ca2+]O induced by different methods.

Journal Article
TL;DR: The morphological and functional aspects of the altered protein metabolism during epileptogenesis are discussed.
Abstract: Epileptogenic mirror focus was produced in the left parietal area of the rat brain by cobalt implantation into the contralateral hemisphere. On the 14th day after cobalt implantation [3H]proline was injected into both experimental and control rats (without cobalt). The incorporation of [3H]proline in neurons of layers III and V of the parietal brain cortex and neurons of the nucleus lateralis thalami was investigated by the autoradiography technique. A statistically reliable increase in [3H]proline uptake was observed in neurons of layer III (31%) and in neurons of layer V (41%) of the epileptogenic mirror focus. The other neuronal types revealed no reliable changes. The morphological and functional aspects of the altered protein metabolism during epileptogenesis are discussed.

Journal Article
TL;DR: It is demonstrated that each structure in the brain has a regional own threshold for Pc induced epileptiform afterdischarge, as demonstrated in the study of epileptogenesis.
Abstract: Investigation of the regional threshold for epilepsy in many structures in the brain would contribute to the study of epileptogenesis. So we studied the threshold for epileptiform afterdischarge in the neocortex, hippocampus and cerebellar cortex using Na-Penicillin -G (Pc) of which epileptogenesis has been intensively investigated. In order to eliminate the influence from the outside of these structures, the brain slice method was utilized. Procedures for preparation of the tissue and incubation were about the same as those described by Yamamoto. In summary, after sacrifice, brain of the guinea pig was taken out and the hippocampus, neocortex and cerebellum were cut with a razor blade under a microscope. The thickness of the section was about 0.3 mm. Slices were incubated at 37 degrees C for about 30 min in the standard medium perfused with 95% O2 and 0% CO2. The chamber was continuously perfused with the standard medium which composed of NaCl, 124 mM, KCl, 5: KH2PO4, 1.24; MgSO4, 1.3; CaCl2, 2.4; NaHCO3, 26; and glucose, 10. Evoked potentials were elicited by electrical stimulation in the standard medium. Mossy fibers were stimulated and responses were recorded from the CA3 area in the hippocampus by glass pipette microelectrode. Subcortical white matter was stimulated and responses were recorded from the Purkinje cell layer in the cerebellum. Pc was added in the standard medium until epileptiform afterdischarges were superimposed on the evoked potentials. The results of this experiment demonstrated that each structure in the brain has a regional own threshold for Pc induced epileptiform afterdischarge.(ABSTRACT TRUNCATED AT 250 WORDS)