Development of Spontaneous Seizures after Experimental Status Epilepticus: Implications for Understanding Epileptogenesis

Williams, Philip A.; Hellier, Jennifer L.; White, Andrew M.; Staley, Kevin J.; Dudek, F. Edward

doi:10.1111/j.1528-1167.2007.01304.x

Cited by 65 publications

(52 citation statements)

References 36 publications

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“…Third, the severity and duration of SE determines the duration of the latency until the first spontaneous seizures. For instance, using continuous video-EEG recordings (with depth electrodes in the dentate gyrus) in the repeated low-dose pilocarpine model that we used in most of our antiepileptogenesis studies, latency to spontaneous seizures is approximately 1 week after SE in most rats (M. Rattka and C. Brandt, unpublished observations) and similar or longer latent periods have been reported by several other studies with continuous monitoring in different post-SE models of TLE (Williams et al, 2007;Sloviter, 2008). In this respect, it is important to note that the 688 LÖSCHER AND BRANDT duration of the latent period depends on the type of induction and severity of the initial SE, ranging from approximately 7 days in the pilocarpine model (Goffin et al, 2007) to Ͼ30 days in models with electrical induction of SE (Nissinen et al, 2000).…”

Section: Problems Associated With Drug Testing In Post-status Epileptsupporting

confidence: 74%

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Löscher¹,

Brandt²

2010

Pharmacol Rev

361

366

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Section: Problems Associated With Drug Testing In Post-status Epileptsupporting

confidence: 74%

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Löscher¹,

Brandt²

2010

Pharmacol Rev

361

366

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“…The key points are: (1) learning destabilizes both the activity and connectivity of a neural system, (2) there is a certain level of connectivity, called critical connectivity, that optimizes brain performance, and (3) there are homeostatic mechanisms that maintain stable levels of activity and critical connectivity in the face of the destabilizing effects of learning.…”

Section: Background: Hebbian Learning Neuronal Avalanches and Criticmentioning

confidence: 99%

“…There is an enormous number of ways in which plasticity can go wrong at all levels of description [2][3][4][5][6][7][8][9]. Particularly at the genetic level, the process of epileptogenesis is a bewildering complex with many contributory factors.…”

Section: Introductionmentioning

confidence: 99%

An open hypothesis: Is epilepsy learned, and can it be unlearned?

Hsu

Chen²,

M³

et al. 2008

Epilepsy & Behavior

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Plasticity is central to the ability of a neural system to learn and also to its ability to develop spontaneous seizures. What is the connection between the two? Learning itself is known to be a destabilizing process at the algorithmic level. We have investigated necessary constraints on a spontaneously active Hebbian learning system and find that the ability to learn appears to confer an intrinsic vulnerability to epileptogenesis on that system. We hypothesize that epilepsy arises as an abnormal learned response of such a system to certain repeated provocations. This response is a network level effect. If epilepsy really is a learned response, then it should be possible to reverse it, i.e., to unlearn epilepsy. Unlearning epilepsy may then provide a new approach to its treatment.

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“…These alterations include increased excitation and decreased inhibition of hippocampal and cortical principal neurons (Cobos et al 2005;FIG. (Xiang et al 2006). Rats injected with kainic acid have been extensively studied as a model of temporal lobe epilepsy (TLE; Williams et al 2007). These animals, after a latent period, exhibit spontaneous, unprovoked seizures and share many elements of hippocampal pathology with human TLE patients, including loss of neurons in the dentate gyrus, mossy fiber sprouting, and hyperexcitability of CA1 pyramidal neurons (Dudek et al 2002;Wenzel et al 2000;Williams et al 2007).…”

Section: Gabaergic Inputs To Interneurons In Epilepsy and Brain Malfomentioning

confidence: 99%

“…Rats injected with kainic acid have been extensively studied as a model of temporal lobe epilepsy (TLE; Williams et al 2007). These animals, after a latent period, exhibit spontaneous, unprovoked seizures and share many elements of hippocampal pathology with human TLE patients, including loss of neurons in the dentate gyrus, mossy fiber sprouting, and hyperexcitability of CA1 pyramidal neurons (Dudek et al 2002;Wenzel et al 2000;Williams et al 2007). Relevant to the studies described here, Morin and colleagues (1999), using electron microscopy, found layer-specific alterations in GABA synapses onto CA1 interneurons in kainic acid-injected rats.…”

Section: Gabaergic Inputs To Interneurons In Epilepsy and Brain Malfomentioning

confidence: 99%

Inhibitory Inputs to Hippocampal Interneurons Are Reorganized in Lis1 Mutant Mice

Jones

Baraban²

2009

Journal of Neurophysiology

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Jones DL, Baraban SC. Inhibitory inputs to hippocampal interneurons are reorganized in Lis1 mutant mice. J Neurophysiol 102: 648 -658, 2009. First published June 10, 2009 doi:10.1152/jn.00392.2009. Epilepsy and brain malformation are commonly associated with excessive synaptic excitation and decreased synaptic inhibition of principal neurons. However, few studies have examined the state of synaptic inhibition of interneurons in an epileptic, malformed brain. We analyzed inhibitory inputs, mediated by ␥-aminobutyric acid (GABA), to hippocampal interneurons in a mouse model of type 1 lissencephaly, a neurological disorder linked with severe seizures and brain malformation. In the disorganized hippocampal area CA1 of Lis1 ϩ/Ϫ mice, we initially observed a selective displacement of fast-spiking, parvalbumin-positive basket-type interneurons from stratum oriens (SO) locations to s. radiatum and s. lacunosum-moleculare (R/LM). Next, we recorded spontaneous and miniature inhibitory postsynaptic currents (sIPSCs and mIPSCs) onto visually identified interneurons located in SO or R/LM of Lis1 ϩ/Ϫ mice and age-matched littermate controls. We observed significant, layer-specific reorganizations in GABAergic inhibition of interneurons in Lis1 mutant mice. Spontaneous IPSC frequency onto SO interneurons was significantly increased in hippocampal slices from Lis1 ϩ/Ϫ mice, whereas mIPSC mean amplitude onto these interneurons was significantly decreased. In addition, the weighted decay times of sIPSCs and mIPSCs were significantly increased in R/LM interneurons. Taken together, these findings illustrate the extensive redistribution and reorganization of inhibitory connections between interneurons that can take place in a malformed brain. I N T R O D U C T I O NEpilepsy, a neurological disorder defined by the presence of spontaneous, unprovoked seizures, is often associated with a brain malformation. These malformations can result from mutations in genes that encode molecular machinery required for proper brain development (Guerrini and Filippi 2005;Guerrini and Marini 2006). In humans, mutations in cytoskeletonassociated proteins such as LIS1, doublecortin, reelin, and ARX have been implicated in a condition known as lissencephaly, the hallmarks of which include a smooth cortical surface, disorganized cortical layering, enlarged ventricles, mental retardation, and severe epilepsy. Brain malformations in lissencephaly are consistent with known functions of these proteins, which include important roles in the process by which microtubules and microtubule-associated motor proteins regulate neuronal migration (Kato and Dobyns 2003;Tsai et al. 2005).Although neuronal migration disorders (NMDs) are widely recognized as a pathology underlying epilepsy and cognitive dysfunction (Guerrini and Filippi 2005), how network function is disrupted when neurons migrate incorrectly is largely unknown. Previous studies of circuit changes associated with NMDs have primarily focused on neocortical malformations; characterizations of hippocampal ma...

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Development of Spontaneous Seizures after Experimental Status Epilepticus: Implications for Understanding Epileptogenesis

Cited by 65 publications

References 36 publications

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

Prevention or Modification of Epileptogenesis after Brain Insults: Experimental Approaches and Translational Research

An open hypothesis: Is epilepsy learned, and can it be unlearned?

Inhibitory Inputs to Hippocampal Interneurons Are Reorganized in Lis1 Mutant Mice

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