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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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Journal ArticleDOI
TL;DR: These findings support the long-standing hypothesis that newly generated dentate granule cells are pro-epileptogenic and contribute to the occurrence of seizures and provide the first proof-of-concept data demonstrating that granule cell ablation therapy applied at a clinically relevant time point after injury can have disease-modifying effects in epilepsy.
Abstract: Hippocampal granule cells generated in the weeks before and after an epileptogenic brain injury can integrate abnormally into the dentate gyrus, potentially mediating temporal lobe epileptogenesis Previous studies have demonstrated that inhibiting granule cell production before an epileptogenic brain insult can mitigate epileptogenesis Here, we extend upon these findings by ablating newly generated cells after the epileptogenic insult using a conditional, inducible diphtheria-toxin receptor expression strategy in mice Diphtheria-toxin receptor expression was induced among granule cells born up to 5 weeks before pilocarpine-induced status epilepticus and these cells were then eliminated beginning 3 d after the epileptogenic injury This treatment produced a 50% reduction in seizure frequency, but also a 20% increase in seizure duration, when the animals were examined 2 months later These findings provide the first proof-of-concept data demonstrating that granule cell ablation therapy applied at a clinically relevant time point after injury can have disease-modifying effects in epilepsy SIGNIFICANCE STATEMENT These findings support the long-standing hypothesis that newly generated dentate granule cells are pro-epileptogenic and contribute to the occurrence of seizures This work also provides the first evidence that ablation of newly generated granule cells can be an effective therapy when begun at a clinically relevant time point after an epileptogenic insult The present study also demonstrates that granule cell ablation, while reducing seizure frequency, paradoxically increases seizure duration This paradoxical effect may reflect a disruption of homeostatic mechanisms that normally act to reduce seizure duration, but only when seizures occur frequently

56 citations

Journal ArticleDOI
TL;DR: Behavioral deficits, together with a non-invasive marker of astrocyte activation, predict which rats develop epilepsy after an acute injury, and have potential clinical relevance for identifying individuals at-risk for developing epilepsy following exposure to epileptogenic insults, and consequently, for designing adequately powered antiepileptogenesis trials.

56 citations

Journal ArticleDOI
TL;DR: Quantifying gamma-band activity during interictal periods and seizures in intracranial EEG (iEEG) in 5 patients implanted with subdural grids/intracranial electrodes during their pre-surgical evaluation suggests that the persistent presence of abnormally intensified gamma rhythms in the EEG may be an important tool for focus localization and possibly a determinant of epileptogenesis.
Abstract: Even though recent studies have suggested that seizures do not occur suddenly and that before a seizure there is a period with an increased probability of seizure occurrence, neurophysiological mechanisms of interictal and pre-seizure states are unknown. The ability of mathematical methods to provide much more sensitive tools for the detection of subtle changes in the electrical activity of the brain gives promise that electrophysiological markers of enhanced seizure susceptibility can be found even during interictal periods when EEG of epilepsy patients often looks 'normal'. Previously, we demonstrated in animals that hippocampal and neocortical gamma-band rhythms (30-100 Hz) intensify long before seizures caused by systemic infusion of kainic acid. Other studies in recent years have also drawn attention to the fast activity (>30 Hz) as a possible marker of epileptogenic tissue. The current study quantified gamma-band activity during interictal periods and seizures in intracranial EEG (iEEG) in 5 patients implanted with subdural grids/intracranial electrodes during their pre-surgical evaluation. In all our patients, we found distinctive (abnormal) bursts of gamma activity with a 3 to 100 fold increase in power at gamma frequencies with respect to selected by clinicians, quiescent, artifact-free, 7-20 min "normal" background (interictal) iEEG epochs 1 to 14 hours prior to seizures. Increases in gamma activity were largest in those channels which later displayed the most intensive electrographic seizure discharges. Moreover, location of gamma-band bursts correlated (with high specificity, 96.4% and sensitivity, 83.8%) with seizure onset zone (SOZ) determined by clinicians. Spatial localization of interictal gamma rhythms within SOZ suggests that the persistent presence of abnormally intensified gamma rhythms in the EEG may be an important tool for focus localization and possibly a determinant of epileptogenesis.

56 citations

Book ChapterDOI
TL;DR: To develop an effective therapeutic strategy that can interfere with the process of development of epilepsy (epileptogenesis), it is crucial to study the changes that occur in the brain after an injury and before epilepsy develops.
Abstract: Epilepsy is one of the most common neurological conditions that affect people of all ages. Epilepsy is characterized by occurrence of spontaneous recurrent seizures. Currently available drugs are ineffective in controlling seizures in approximately one-third of patients with epilepsy. Moreover, these drugs are associated with adverse effects, and none of them are effective in preventing development of epilepsy following an insult or injury. To develop an effective therapeutic strategy that can interfere with the process of development of epilepsy (epileptogenesis), it is crucial to study the changes that occur in the brain after an injury and before epilepsy develops. It is not possible to determine these changes in human tissue for obvious ethical reasons. Over the years, experimental models of epilepsies have contributed immensely in improving our understanding of mechanism of epileptogenesis as well as of seizure generation. There are many models that replicate at least some of the characteristics of human epilepsy. Each model has its advantages and disadvantages, and the investigator should be aware of this before selecting a specific model for his/her studies. Availability of a good animal model is a key to the development of an effective treatment. Unfortunately, there are many epilepsy syndromes, specifically pediatric, which still lack a valid animal model. It is vital that more research is done to develop animal models for such syndromes.

56 citations

Journal ArticleDOI
TL;DR: Investigating pathological alterations in GABAergic interneurons in the rat basolateral amygdala (BLA) and the functional impact of these alterations on inhibitory synaptic transmission, on days 7 to 10 after status epilepticus induced by kainic acid found a dramatic reduction of tonic inhibitory activity.

56 citations


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Performance
Metrics
No. of papers in the topic in previous years
YearPapers
2023181
2022348
2021245
2020219
2019210
2018209