Generalized absence epilepsy and catalepsy in rats

Kuznetsova, G. M.; Петрова, Е В; Coenen, A.M.L.; Luijtelaar, E.L.J.M. van

doi:10.1016/0031-9384(96)00175-8

Cited by 28 publications

(12 citation statements)

References 24 publications

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“…Enhanced susceptibility to catalepsy was found even in young (8-week-old) WAG/Rij rats in which SWDs could not yet be detected (Kuznetsova et al, 1996). This indicates that the dopaminergic deficiency appears prior to the development of absence seizures and therefore could not be attributed solely to a consequence of repeated absence seizures but directly associated with the appearance of absence seizures.…”

Section: Dopaminementioning

confidence: 72%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

128

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Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development.Neuroscience and Biobehavioral Reviews http://dx.doi.org/10. 1016/j.neubiorev.2016.09.017 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractThe WAG/Rij rat model has recently gathered attention as a suitable animal model of absence epileptogenesis. This latter term has a broad definition encompassing any possible cause that determines the development of spontaneous seizures; however, most of, if not all, preclinical knowledge on epileptogenesis is confined to the study of post-brain insult models such as traumatic brain injury or post-status epilepticus models. WAG/Rij rats, but also synapsin 2 knockout, Kv7 current-deficient mice represent the first examples of genetic models where an efficacious antiepileptogenic treatment (ethosuximide) was started before seizure onset. In this review, we have critically reconsidered all articles published regarding WAG/Rij rats, from the perspective that the period before SWD onset is considered as the latent period. In our new theory on seizure development, it is proposed that genes might be considered as the initial "insult" responsible for all plastic changes underpinning the development of spontaneous seizures. According to this idea, in WAG/Rij rats, genetic predisposition would lead to the development of abnormal bilateral cortical epileptic foci, which would then nongenetically stimulate the rest of the brain to rearrange networks in order to phenotypically develop seizures similarly to what happens during electrical kindling.

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Section: Dopaminementioning

confidence: 72%

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Russo

Citraro

Constanti³

et al. 2016

Neuroscience & Biobehavioral Reviews

128

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“…These EEG graphoelements were distinguishable from sleep spindles (10-16 Hz), regarding their frequency, duration, morphology (sleep spindles are more stereotyped than SWD waves), and moment of occurrence (SWD occurs during passive wakefulness versus sleep spindle-like oscillation occurring during high amplitude delta activity (Kuznetsova et al 1996;Pinault et al 2001). Similar to the reports that bilateral generalized synchronous SWD could be 5-7 Hz and lasting around 1 s (Kitada et al 2000) or with frequency range of about 8 Hz, with 5 s duration (van Luijtelaar and Coenen 1986), we found a characteristic frequency of 6-8 (7) Hz in EEG during the absence seizure.…”

Section: Discussionmentioning

confidence: 99%

“…It can be speculated that this might be due to the activation of the same brain stem mechanism responsible for the behavioral inactivity belonging to catalepsy (Kuznetsova et al 1996).…”

Section: Discussionmentioning

confidence: 99%

“…The inclusion criteria for the analyzed spike-andwave discharge (SWD) data were as follows: (1) spontaneous and generalized, rhythmic 5-7 Hz discharges; (2) with typical spike-wave complex lasting [1 s; and (3) amplitude of at least twice the background EEG activity (van Luijtelaar and Coenen 1986;Kuznetsova et al 1996;Pinault et al 2001;Schridde and van Luijtelaar 2004;Yan et al 2005;Sitnikova and van Luijtelaar 2007;Blumenfeld et al 2008). The number and duration of SWDs were calculated at 15-min intervals during 90-min period after H injection.…”

Section: Eeg/swd Recordingsmentioning

confidence: 99%

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Two Types of Seizures in Homocysteine Thiolactone-Treated Adult Rats, Behavioral and Electroencephalographic Study

et al. 2008

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D,L-homocysteine thiolactone (H), a reactive homocysteine metabolite, contributes to total homocysteine pool. The aim of the present study was to determine the effects of H after acute application in increasing doses to rats. Adult Wistar rat were intraperitoneally administered saline or H in increasing doses (5.5, 8.0, or 11.0 mmol/kg). For electroencephalographic (EEG) recordings, three gold-plated screws were implanted into the skull and animals were supervised. We observed H-induced two types of seizures, the coexistence of convulsive and nonconvulsive epilepsy. Dose-related increase in the number and severity (0-4) of displaying convulsions was recorded. In H(5.5) group, the majority of seizure episodes were grade 1 (62.5 and 0% lethality), in H(8) 40% grade 2, and in H(11) grade 4 in 42.11% (100% lethal outcome). EEGs recordings in convulsive animals showed a high-voltage spike-wave and polyspikes complexes. The second, absence-like, nonconvulsive seizures were accompanied by the EEGs mostly with 6-8 Hz spikes-and-wave discharges (SWD). Latency time to the generalized clonic-tonic seizures overlapped with the time of the maximal median number and median duration of the SWD per 15 min during 90-min observing period. The results show that acute H administration significantly changes neurons, EEG tracings, and behavioral responses and suggests a possible model for studying petit mal epilepsy.

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“…WAG/Rij rats were housed three/four per cage and kept under stable environmental conditions, humidity (60 ± 5%) and temperature (21 ± 2 °C), in a room with 12/12 h reversed light/dark cycle (lights on at 20.00). WAG/Rij rats at 27 days of age (P27) were screened, as previously described [37,38], to evaluate their susceptibility to audiogenic stimuli. Afterwards, only rats without audiogenic susceptibility were used in experiments, considering that WAG/Rij rats expressing audiogenic seizures display higher levels of anxiety in comparison to non-audiogenic WAG/Rij rats [26].…”

Section: Animalsmentioning

confidence: 99%

Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

et al. 2017

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One of the major challenges in the epilepsy field is identifying disease-modifying drugs in order to prevent or delay spontaneous recurrent seizure onset or to cure already established epilepsy. It has been recently reported that fingolimod, currently approved for the treatment of relapsing-remitting multiple sclerosis, has demonstrated antiepileptogenic effects in two different preclinical models of acquired epilepsy. However, to date, no data exist regarding the role of fingolimod against genetic epilepsy. Therefore, we have addressed this issue by studying the effects of fingolimod in WAG/Rij rats, a well-established genetic model of absence epilepsy, epileptogenesis, and neuropsychiatric comorbidity. Our results have demonstrated that an early-long term treatment with fingolimod (1 mg/Kg/day), started before absence seizure onset, has both antiepileptogenic and antidepressant-like effects in the WAG/Rij rats. However, these effects were transitory, since 5 months after treatment discontinuation, both absence seizure and depressive like-behavior returned to control level.Furthermore, a temporary reduction of mTOR signaling pathway activity, indicated by reduced p-mTOR and p-p70S6k levels and by an increased p-AKT in WAG/Rij rats of 6 months of age accompanied the transitory antiepileptogenic fingolimod effects. Surprisingly, fingolimod has demonstrated longer-lasting positive effects on cognitive decline in this strain. This effect was accompanied by an increased acetylation of Lysine 8 of histone H4 (both 6 and 10 months of age). In conclusion, our results support the antiepileptogenic effects fingolimod. However, these antiepileptogenic effects were transitory. Moreover, fingolimod might also have a positive impact on animal behavior and particularly in protecting the development of memory decline.

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Generalized absence epilepsy and catalepsy in rats

Cited by 28 publications

References 24 publications

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Upholding WAG/Rij rats as a model of absence epileptogenesis: Hidden mechanisms and a new theory on seizure development

Two Types of Seizures in Homocysteine Thiolactone-Treated Adult Rats, Behavioral and Electroencephalographic Study

Fingolimod Exerts only Temporary Antiepileptogenic Effects but Longer-Lasting Positive Effects on Behavior in the WAG/Rij Rat Absence Epilepsy Model

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