Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy

Bouilleret, Viviane; Ridoux, V.; Depaulis, Antoine; Marescaux, Christian; Nehlig, Astrid

doi:10.1016/s0306-4522(98)00401-1

Cited by 398 publications

(492 citation statements)

References 63 publications

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“…Once established, this activity is not associated with motor convulsions, it is stable, and it is refractory to phenytoin, carbamazepine, and valproate [24], thus providing a model for focal epilepsy not responding to some commonly used AEDs [24,25,[27][28][29]. Histopathological changes are restricted to the hippocampus injected with kainate and are similar to those described in human mesial TLE including neuronal loss, granule cell dispersion, and sprouting [23][24][25][27][28][29].…”

Section: Chronic Epileptic Micementioning

confidence: 81%

“…We used a chronic model of spontaneous epileptic activity that has been extensively described before [23][24][25][27][28][29], which develops in mice following nonconvulsive status epilepticus (SE) lasting for as long as 10 h, induced by unilateral intrahippocampal application of 200 ng in 50 nl kainic acid. Spontaneous epileptic activity reproducibly occurs after 3 to 7 days on average from SE induction ("for more detail see as follows") and it recurs for several months.…”

Section: Chronic Epileptic Micementioning

confidence: 99%

“…The objective of this study was to establish whether ICE/caspase-1 inhibition by VX-765 could suppress spontaneous recurrent epileptic activity by using a mouse model, which recapitulates some of the salient neuropathological sequelae of TLE, and in which epileptic activity does not respond to some commonly used antiepileptic drugs (AEDs) [23,24]. Moreover, because VX-765 effect on acute seizures was previously studied only in rats, we extended this investigation to mice injected with kainic acid, because this model involves the activation of ICE/caspase-1 [9].…”

Section: Introductionmentioning

confidence: 99%

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Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

et al. 2011

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Summary: Experimental evidence and clinical observations indicate that brain inflammation is an important factor in epilepsy. In particular, induction of interleukin-converting enzyme (ICE)/caspase-1 and activation of interleukin (IL)-1β/ IL-1 receptor type 1 axis both occur in human epilepsy, and contribute to experimentally induced acute seizures. In this study, the anticonvulsant activity of VX-765 (a selective ICE/ caspase-1 inhibitor) was examined in a mouse model of chronic epilepsy with spontaneous recurrent epileptic activity refractory to some common anticonvulsant drugs. Moreover, the effects of this drug were studied in one acute model of seizures in mice, previously shown to involve activation of ICE/caspase-1. Quantitative analysis of electroencephalogram activity was done in mice exposed to acute seizures or those developing chronic epileptic activity after status epilepticus to assess the anticonvulsant effects of systemic administration of VX-765.Histological and immunohistochemical analysis of brain tissue was carried out at the end of pharmacological experiments in epileptic mice to evaluate neuropathology, glia activation and IL-1β expression, and the effect of treatment. Repeated systemic administration of VX-765 significantly reduced chronic epileptic activity in mice in a dose-dependent fashion (12.5-200 mg/kg). This effect was observed at doses ≥50 mg/ kg, and was reversible with discontinuation of the drug. Maximal drug effect was associated with inhibition of IL-1β synthesis in activated astrocytes. The same dose regimen of VX-765 also reduced acute seizures in mice and delayed their onset time. These results support a new target system for anticonvulsant pharmacological intervention to control epileptic activity that does not respond to some common anticonvulsant drugs.

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Section: Chronic Epileptic Micementioning

confidence: 81%

Section: Chronic Epileptic Micementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

et al. 2011

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“…In this model, SE is induced by unilateral injection of kainate into the CA1 sector of the dorsal hippocampus 15, 16. For this purpose, mice were anesthetized with chloral hydrate (400–500 mg/kg i.p.…”

Section: Methodsmentioning

confidence: 99%

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain

Twele¹,

Töllner²,

Bankstahl³

et al. 2016

Epilepsia Open

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SummaryObjectiveMesial temporal lobe epilepsy (TLE) with hippocampal sclerosis is a predominant form of acquired epilepsy, characterized by recurrent simple and complex partial seizures that are often resistant to treatment. Mice developing spontaneous recurrent nonconvulsive and convulsive seizures after intrahippocampal injection of the excitotoxic glutamate agonist kainate are thought to represent a valuable model of mesial TLE. Epileptic electroencephalogram (EEG) activity recorded in this model from the kainate focus in the ipsilateral hippocampus is resistant to antiseizure drugs such as carbamazepine (CBZ). We compared the efficacy of CBZ in this model in two different mouse strains (FVB/N and NMRI). Furthermore, we evaluated whether changes in the definition of electrographic seizures affect the antiseizure efficacy of CBZ.MethodsAs in previous studies, two types of epileptic EEG activity were defined: high‐voltage sharp waves (HVSWs) and hippocampal paroxysmal discharges (HPDs). The characteristics of these paroxysmal EEG events in epileptic mice were compared with EEG criteria for nonconvulsive seizures in patients. For HVSWs, different spike frequencies, interevent intervals, and amplitudes were used as inclusion and exclusion criteria. In addition to CBZ, some experiments were performed with diazepam (DZP) and phenobarbital (PB).ResultsFemale epileptic FVB/N mice predominantly exhibited frequent HVSWs, but only infrequent HPDs or secondarily generalized convulsive seizures. Slight changes in HVSW definition determined whether they were resistant or responsive to CBZ. Male NMRI mice exhibited both HVSWs and HPDs. HVSWs were more resistant than HPDs to suppression by CBZ. Both types of epileptic EEG activity were rapidly suppressed by DZP and PB.SignificanceThe data demonstrate that focal electrographic seizures in the intrahippocampal kainate mouse model are less resistant than previously thought. Both mouse strain and the criteria chosen for definition of EEG seizures determine whether such seizures are drug‐resistant or ‐responsive.

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“…For this study, an adult mouse (male, 8 weeks old) was subjected to an intra-hippocampal injection of the glutamate agonist kainic acid (KA, 1nmol of KA in 50 nL, Sigma-Aldrich, St Louis, MO, USA), an experimental model that reliably reproduces the physiopathological features observed in human MTLE 10, 11 .…”

Section: Methodsmentioning

confidence: 99%

Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy

et al. 2015

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Brain Functional Connectivity (FC) quantifies statistical dependencies between areas of the brain.FC has been widely used to address altered function of brain circuits in control conditions compared to different pathological states, including epilepsy, a major neurological disorder. However, FC also has the as yet unexplored potential to help us understand the pathological transformation of the brain circuitry.Our hypothesis is that FC can differentiate global brain interactions across a time-scale of days. To this end, we present a case report study based on a mouse model for epilepsy and analyze longitudinal intracranial electroencephalography data of epilepsy to calculate FC across three stages: 1, the initial insult (status epilepticus); 2, the latent period, when epileptogenic networks emerge; and 3, chronic epilepsy, when unprovoked seizures occur as spontaneous events.We found that the overall network FC at low frequency bands decreased immediately after status epilepticus was provoked, and increased monotonously later on during the latent period. Overall, our results demonstrate the capacity of FC to address longitudinal variations of brain connectivity across the establishment of pathological states.

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Recurrent seizures and hippocampal sclerosis following intrahippocampal kainate injection in adult mice: electroencephalography, histopathology and synaptic reorganization similar to mesial temporal lobe epilepsy

Cited by 398 publications

References 63 publications

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

Interleukin-1β Biosynthesis Inhibition Reduces Acute Seizures and Drug Resistant Chronic Epileptic Activity in Mice

The effects of carbamazepine in the intrahippocampal kainate model of temporal lobe epilepsy depend on seizure definition and mouse strain

Longitudinal variations of brain functional connectivity: A case report study based on a mouse model of epilepsy

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