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Wiley InterScience | |||||||||
  EpilepsiaVolume 47 Issue 2, Pages 227 - 228 Published Online: 24 Feb 2006 © 2010 International League Against Epilepsy Published on behalf of the International League Against Epilepsy (ILAE)
Abstract | Full Text: PDF (Size: 146K) | Related Articles | Citation Tracking  Basic Science Copyright 2006 International League Against Epilepsy Influence of Lamotrigine and Topiramate on MDR1 Expression in Difficult-to-Treat Temporal Lobe Epilepsy Epilepsia 2006;47(2). ABSTRACTYing Wang-Tilz, Christian Tilz, Bing Wang, Gernot P. Tilz, and Hermann Stefan Some individuals with epilepsy appear resistant to most or all antiepileptic medications. One possible explanation for this resistance is the presence of a gene called MDR1 that causes production in the brain of a substance called p-glycoprotein (P-gp). We studied a model of epilepsy in rats produced by repeated injections of Coriaria lactone, an epileptogenic plant toxin. The clinical antiepileptic drugs, topiramate and lamotrigine, significantly reduced seizures. With these two drugs, P-gp was not increased in brain. In contrast, carbamazepine and valproate did increase brain P-gp, and these drugs were less beneficial against the seizures. These results suggest that attention could usefully be paid to whether medications activate multiple drug-resistance genes in brain, because such an effect could counteract the effectiveness of a medication. Serotonin Depletion Attenuates AY-9944–Mediated Atypical Absence Seizures Epilepsia 2006;47(2). ABSTRACTEduard Bercovici, Miguel A. Cortez, Xiaomei Wang, and O. Carter Snead III Atypical absence seizures (AASs) are among the most debilitating types of childhood epilepsies. They usually coexist with other seizure types, are refractory to medications, and are associated with cognitive deficits. AASs are reproducible in rats and mice by administration of the cholesterol inhibitor AY-9944 (AY) to developing pups, leading to chronic seizures with slow spike–wave discharge (SSWD) morphology. Seizures in AY-treated rats are worsened during slow-wave sleep, where SSWDs become continuous, and myoclonic jerks appear more frequently. This effect of sleep suggests that serotonin (5-HT) may be involved in modulating epileptic seizures in the AY model. To investigate the role of serotonin, we studied AY-treated rats with implanted cortical electrodes, and depleted serotonin via administration of para-chlorophenylalanine (PCPA). SSWDs were measured before and after serotonin depletion, after which brains were removed for biochemical analysis via high-performance liquid chromatography (HPLC). We found that PCPA decreased the total duration of SSWDs in AY rats as compared with controls. In addition, we confirmed that PCPA depleted serotonin and its metabolite (5-HIAA) in all brain regions studied. Furthermore, we showed that naive AY rats had elevated 5-HT and 5-HIAA as compared with controls. Our data show that serotonin depletion protects against atypical absence seizures and suggest that high serotonin levels may be involved in the pathogenesis of these seizures. These results could suggest strategies to develop antiepileptic medications that reduce serotonin effects, and also could introduce a caution in using drugs that increase serotonin in patients with atypical absence epilepsy. A Brief Period of Epileptiform Activity Strengthens Excitatory Synapses in the Rat Hippocampus in Vitro Epilepsia 2006;47(2). ABSTRACTDominique Debanne, Scott M. Thompson, and Beat H. Gähwiler A sizeable fraction of all human epilepsies are acquired by otherwise healthy individuals as the result of injury or illness. In many of these acquired epilepsies, the initial insult is associated with a brief period of seizures, which is then followed by a long latent period before the patient truly has epilepsy. We examined here whether a very short period of epileptiform (seizure) activity could produce lasting modifications of synaptic strength and network properties in the rat hippocampus slice, kept alive in a dish. Hippocampus is useful to study because it is the most seizure-prone part of brain, and its circuitry is well studied. Synaptic transmission at two types of synapse was monitored in hippocampal slice cultures before and after a very brief episode of epileptiform activity (20–180 s) induced with bicuculline methochloride, a blocker of inhibitory synaptic transmission. We show here that a very brief period of epileptiform activity induces long-lasting (>20 min) potentiation of excitatory synaptic transmission. This potentiation also was observed at synapses formed by pairs of connected neurons. It was dependent on activation of the N-methyl-d-aspartate (NMDA) subtype of the glutamate receptor, a receptor that is involved in learning and memory. Interestingly, the enhancement of synaptic transmission could be reversed by a specific regime of stimulation. Recruitment of synaptic networks within the hippocampus was facilitated after epileptiform activity, indicating that the induced potentiation enhanced overall hippocampal network excitability. These changes in synaptic transmission may contribute to the genesis of epilepsy and to seizure-associated memory deficits. Reeler Homozygous Mice Exhibit Enhanced Susceptibility to Epileptiform Activity Epilepsia 2006;47(2). ABSTRACTPeter R. Patrylo, Ronald A. Browning, and Scott Cranick Humans with diffuse cortical malformations (CMs) are observed frequently to have impaired cognitive development, epilepsy, and other neurologic disorders. Several animal models are available currently that exhibit diffuse CNS disruptions. However, in contrast to the human condition, enhanced seizure susceptibility has been reported in only a handful of these models. Whether this disparity reflects a difference in the phenotypic properties of these models that can be used to delineate the mechanisms involved with increasing seizure susceptibility, or reflects a paucity of knowledge, is unclear. Consequently, in this study, a combination of in vivo and in vitro techniques was used to determine whether seizure susceptibility is altered in reeler mutant mice (rl/rl); a model of CM that exhibits anatomic alterations and a mode of inheritance similar to that found in a human condition (lissencephaly with cerebellar hypoplasia; LCH). In vivo experiments revealed that rl/rl mice, compared with controls, exhibit a lower threshold for seizures and a higher incidence of seizures when subjected to comparable stimuli. Studies of brain slices maintained alive in a dish revealed that compared with controls, malformed cortical regions from rl/rl mice were more likely to generate spontaneous epileptiform activity when inhibition was compromised, and that the duration of these events was longer. Considered together, these data indicate that rl/rl mice have enhanced seizure susceptibility that is in part intrinsic to the malformed cortical regions. Moreover, these findings indicate that the reeler mutant mouse may provide a valuable model of CM because of their similarities to the human condition of LCH. Diacylglycerol Kinase Epsilon Modulates Rapid Kindling Epileptogenesis Epilepsia 2006;47(2). ABSTRACTAlberto Musto and Nicolas G. Bazan The development of mesial temporal lobe epilepsy progresses from partial complex seizures and is followed by secondarily generalized seizures. In turn, this can lead to seizure recurrence that causes mental and learning disabilities, psychosocial problems, and unresponsiveness to antiepileptic drugs. Neuronal signal transduction mediated by the neurotransmitter glutamate is believed to be a major pathway by which seizures develop and become more severe. A family of enzymes known as the diacylglycerol kinases participates in glutamate-mediated signaling through the regulation of a fatty (lipid) signaling system based on the compound, inositol. One form of the diacylglycerol kinase enzyme, called the epsilon isoform, specifically recognizes inositol lipids that contain arachidonic acid. It has long been known that arachidonic acid is liberated from brain cell membranes during seizures, stroke, and other forms of neural injury, and this free fatty acid is rapidly converted to a cascade of signaling molecules that propagates and magnifies the initial cellular injury. Mice deficient in the diacylglycerol kinase gene subjected to an experimental model of mesial temporal lobe epilepsy displayed attenuated development and progression of epileptic seizures. Furthermore, the microscopic alterations in brain synapses that are characteristic of epileptogenesis are decreased or absent when this gene is not active. The significance of this discovery lies in its identification of a molecular pathway that potentially can be used for the targeting of antiseizure medications. Decrease of Hippocampal GABA Epilepsia 2006;47(2). ABSTRACTMin-Lan Tsai and L. Stan Leung We studied the consequences of heat-induced seizures in immature rat pups, 13 to 15 days after birth, as a model of febrile seizures in children. We hypothesize that neuronal inhibition in the hippocampus, one of the most seizure-prone areas of the brain, is decreased by heat-induced seizures. A single seizure was induced by heating with an infrared lamp (fast heat), or repeated seizures were induced in rat pups (nine seizures over a 3-day period) by a hair dryer (slow heat). Brain wave and behavioral recordings indicate that the hair-dryer–induced seizures were relatively localized to the amygdala and hippocampus, whereas an infrared lamp seizure was more severe and involved extensive areas of the brain, perhaps including the brainstem. However, irrespective of seizure types, long-term physiologic recordings of the rats after the heat-induced seizures indicated that a late neuronal inhibition was lost in certain key regions of the hippocampus. The late neuronal inhibition, shown to be mediated by GABA Neocortical Microenvironment in Patients with Intractable Epilepsy: Potassium and Chloride Concentrations Epilepsia 2006;47(2). ABSTRACTAli Gorji, Nina Stemmer, Bernhard Rambeck, Uwe Jürgens, Theodor May, Heinz Wolfgang Pannek, Friedrich Behne, Alois Ebner, Hiedrun Straub, and Erwin-Josef Speckmann The regulation of extracellular ion concentrations plays an important role in neuronal function and epileptogenesis. Despite the many studies into the mechanisms of epileptogenesis in human experimental models, no data are available regarding the fluctuations of extracellular potassium ([K | 
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