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Epileptogenesis
About: Epileptogenesis is a research topic. Over the lifetime, 4218 publications have been published within this topic receiving 170809 citations.
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TL;DR: The upregulation of NMDA receptors seen in DG and CA3 region of the hippocampus could be associated with the kindling process of this model especially with its maintenance phase, since it persists at long term, is area-specific and consistent with electrophysiological data.
Abstract: "Kindling" is a phenomenon of epileptogenesis, which has been widely used as an experimental model of temporal lobe epilepsy. At the present work we investigated the contribution of NMDA receptors in the Pentylenetetrazol-induced "kindling" model in the mouse brain, by using quantitative autoradiography and the radioactive ligands [3H]MK801 and [3H]L-glutamate (NMDA-sensitive component). One week after establishment of kindling, a small but significant increase in [3H]MK801 as well as NMDA-sensitive [3H]glutamate binding was seen, being restricted to the molecular layer (ML) of the dentate gyrus (DG) and the CA3 region of the hippocampus. These binding augmentations persisted one month after establishment of kindling. A significant increase of NMDA receptor binding was also observed in the cortex-somatosensory and temporal one week after acquisition of the kindled state. The upregulation of NMDA receptors seen in DG and CA3 region of the hippocampus could be associated with the kindling process of this model especially with its maintenance phase, since it persists at long term, is area-specific and consistent with electrophysiological data. The increase of NMDA receptors seen in the cortex of the kindled animals could underlie the hyperexcitability detected by electrophysiological studies in this area.
66 citations
TL;DR: Results indicate that the activated microglia in the epileptic hilus may guide the aberrant migration of newborn neurons and that minocycline could be a potential drug to impede seizure‐induced aberrant migrated neurons.
Abstract: Recent evidence showed that epileptic seizures increase hippocampal neurogenesis in the adult rat, but prolonged seizures result in the aberrant hippocampal neurogenesis that often leads to a recurrent excitatory circuitry and thus contributes to epileptogenesis. However, the mechanism underlying the aberrant neurogenesis after prolonged seizures remains largely unclear. In this study, we examined the role of activated astrocytes and microglia in the aberrant hippocampal neurogenesis induced by status epilepticus. Using a lithium-pilocarpine model to mimic human temporal lobe epilepsy, we found that status epilepticus induced a prominent activation of astrocytes and microglia in the dentate gyrus 3, 7, 14, and 20 days after the initial seizures. Then, we injected fluorocitrate stereotaxicly into the dentate hilus to inhibit astrocytic metabolism and found that fluorocitrate failed to prevent the seizure-induced formation of ectopic hilar basal dendrites but instead promoted the degeneration of dentate granule cells after seizures. In contrast, a selective inhibitor of microglia activation, minocycline, inhibited the aberrant migration of newborn neurons at 14 days after status epilepticus. Furthermore, with stereotaxic injection of lipopolysaccharide into the intact dentate hilus to activate local microglia, we found that lipopolysaccharide promoted the development of ectopic hilar basal dendrites in the hippocampus. These results indicate that the activated microglia in the epileptic hilus may guide the aberrant migration of newborn neurons and that minocycline could be a potential drug to impede seizure-induced aberrant migration of newborn neurons.
66 citations
TL;DR: This study confirms previous reports that surgical outcomes for ETLE epilepsy are significantly worse than those for temporal lobe epilepsy and confirms that more uniform protocols are necessary for fair evaluation and comparison of outcomes among the different centers.
Abstract: Previous small studies have demonstrated that seizure outcomes following surgery for extratemporal lobe epilepsy (ETLE) in children are worse than those for temporal lobe epilepsy. We have conducted a meta-analysis of the available literature to better understand ETLE surgical outcomes in children. We searched PubMed (1990–2009) for appropriate studies using the following terms: ETLE, ETLE surgery, ETLE surgery outcome, frontal lobe epilepsy, occipital lobe epilepsy, and parietal lobe epilepsy. Our collected data included patient age at seizure onset and surgery, the cerebral lobe involved with epileptogenesis, MRI findings, predominant seizure semiology, intracranial monitoring use (electrode implantation), epileptic region histopathology, and postoperative seizure outcome. Statistical analysis was performed to determine associations among these variables and postoperative outcome. Ninety-five patients from 17 studies satisfied the inclusion criteria. Pathological findings (p = 0.039) and seizure type (p = 0.025) were significantly associated with outcome: A larger proportion of patients with cortical dysplasia and complex partial seizures experienced better outcomes. Age at surgery (p = 0.073) and the cerebral resection site (p = 0.059) were marginally associated with seizure outcome. This study confirms previous reports: Surgical outcomes for ETLE epilepsy are significantly worse than those for temporal lobe epilepsy. The reasons for this difference may include the diffuse nature of the pathology involved in ETLE, difficulty in localizing the seizure focus in young children, and involvement of “eloquent” nonresectable cortex in epileptogenesis. Because of the reporting variability among different epilepsy centers, more uniform protocols are necessary for fair evaluation and comparison of outcomes among the different centers.
66 citations
TL;DR: The EXIST-3 trial provided the first evaluation of the optimal dosage, conferring a higher chance of reducing seizure frequency and severity, with adverse events being similar to what observed with lower dosages.
Abstract: Introduction. The mammalian target of rapamycin (mTOR) pathway has emerged as a key player for proper neural network development, and it is involved in epileptogenesis triggered by both genetic or ...
66 citations
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TL;DR: The Cortical Neuron as an Electrophysiological Unit and Cortical Epileptogenesis in the Developing Human Brain are studied.
Abstract: PART I: GENERAL OVERVIEW 1. Thirty Years Among Cortical Neurons PART II: A CELLULAR AND SYNAPTIC PERSPECTIVE OF THE CORTICAL NEURON 2. Cortical Synaptic Transmission: An Overview 3. The Cortical Neuron as an Electrophysiological Unit 4. Signal Transduction and Protein Phosphorylation 5. Structure and Function of Ligand-Gated Channels 6. Synaptic Actions of Amino Acid Neurotransmitters 7. Synaptic Plasticity in Hippocampus and Neocortex: A Comparison PART III: THE CORTICAL NEURON AS PART OF A NETWORK 8. Overview: Basic Elements of the Cortical Network 9. Functions of Local Circuits in Neocortex: Synchrony and Laminae 10. Inhibition in the Cortical Network 11. Thalamocortical Interactions 12. Models of Cortical Networks PART IV: THE DEVELOPING CORTICAL NEURON 13. Determination of Cellular Phenotype and the Fundamental Organization of Cortical Layering: An Overview 14. Neurotransmitter Signaling Before the Birth of Neurons 15. Gene Control of Cortical Excitability 16. Development of Cortical Excitation and Inhibition 17. Cortical Epileptogenesis in the Developing Human Brain PART V. THE VULNERABLE CORTICAL NEURON 18. Glutamate Receptors and Neuronal Death: A Beginning 19. Measurement of Cortical Neurotransmitter Receptors with Radioligand Binding: Insights into the Mechanisms of Kindling-Induced Epilepsy 20. Pathophysiology of Cortical Synapses and Circuits 21. Pathophysiology of Cortical Areas from Human Epileptics 22. Clinical Strategies for Neuronal Protection
66 citations