Chronic levetiracetam treatment early in life decreases epileptiform events in young GAERS, but does not prevent the expression of spike and wave discharges during adulthood

Dedeurwaerdere, Stefanie; Boon, Paul; Smedt, Tim De; Claeys, Pieter W.; Raedt, Robrecht; Bosman, Tommy; Hese, Peter Van; Maele, Georges Van; Vonck, Kristl

doi:10.1016/j.seizure.2005.07.001

Cited by 23 publications

(24 citation statements)

References 29 publications

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“…A significant inhibition of absence- like seizures was observed in LEV-treated SERs compared with controls (59). Recently, similar longlasting antiepileptic effects by LEV have also been observed in genetically absence epilepsy rat from Strasburg (GAERS) (60). Together with our findings, single and repeated administrations of LEV in adult SERs produce unusual long-lasting anti-seizure effects (>4 weeks), which are not considered to be merely due to LEV accumulation in the brain.…”

Section: Antiepileptogenic Effects Of Lev In Serssupporting

confidence: 89%

A New Frontier in Epilepsy: Novel Antiepileptogenic Drugs

Sasa

2006

J Pharmacol Sci

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Abstract. Epilepsy is a hetergenous syndrome characterized by recurrently and repeatedly occurring seizures. Although able to inhibit the epileptic seizures, the currently available antiepileptic drugs (AEDs) have no effects on epileptogenesis. Such AEDs should be classified as drugs against ictogenesis, which are transient events in ion and / or receptor-gated channels related with triggering to evoke seizures. Epileptogenesis involves long-term and histological / biochemical/ physiological alterations formed in brain structures over a long period, ranging from months to years. This review focuses on the effects of AEDs on epileptogenesis and novel candidates of antiepileptogenic drugs using a genetically defined epilepsy model animal, the spontaneous epileptic rat (SER).

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Section: Antiepileptogenic Effects Of Lev In Serssupporting

confidence: 89%

A New Frontier in Epilepsy: Novel Antiepileptogenic Drugs

Sasa

2006

J Pharmacol Sci

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“…However, it has been found that LEV suppressed seizures not only during chronic treatment but also for a long time after its termination. This effect indicating antiepileptogenic activity of LEV has been described in the rat pilocarpine model (Glien et al, 2002), spontaneously epileptic rats (SER) (Yan et al, 2005) and in Genetically Absence Epileptic Rats (GAERS) (Dedeurwaerdere et al, 2005).…”

mentioning

confidence: 64%

“…A potent antiepileptic effect of LEV has been demonstrated in rats kindled with repeated electrical or chemical stimulation (Loscher & Honack, 1993; Klitgaard et al, 1998; Stratton et al, 2003) and in rats genetically prone to convulsive and nonconvulsive seizures (Gower et al, 1995; Bouwman & van Rijn, 2004; Dedeurwaerdere et al, 2005; Ji‐qun et al, 2005). A single injection of LEV induced the maximal antiepileptic effect in about 1 h postinjection.…”

mentioning

confidence: 99%

Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model

Vinogradova

Rijn

2008

Epilepsia

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“…Early treatment of WAG/Rij rats with ethosuximide before the developmental onset of SWD and continued through adulthood was found to suppress seizures and molecular changes usually seen in these rats in adulthood even 3 months after the medication was stopped (Blumenfeld et al, 2008). Early treatment of GAERS for a shorter time period was found to have a similar, but somewhat less strong suppressive effect on SWD epileptogenesis (Dedeurwaerdere et al, 2005). It will be crucial in future studies to test whether early and sustained blockade of SWD in WAG/Rij and GAERS will be sufficient to prevent the observed DTI abnormalities.…”

Section: Discussionmentioning

confidence: 99%

DTI abnormalities in anterior corpus callosum of rats with spike–wave epilepsy

et al. 2009

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Objective Absence epilepsy is a common seizure disorder in children which can produce chronic psychosocial sequelae. Human patients and rat absence models show bilateral spike-wave discharges (SWD) in cortical regions. We employed diffusion tensor imaging (DTI) in rat absence models to detect abnormalities in white matter pathways connecting regions of seizure activity. Methods We studied Wistar albino Glaxo rats of Rijswijk (WAG/Rij), genetic absence epilepsy rats of Strasbourg (GAERS), and corresponding nonepileptic control strains. Ex vivo DTI was performed at 9.4T with diffusion gradients applied in 16 orientations. We compared fractional anisotropy (FA), perpendicular (λ⊥) and parallel (λ∥) diffusivity between groups using t-maps and region of interest (ROI) measurements. Results Adult epileptic WAG/Rij rats exhibited a localized decrease in FA in the anterior corpus callosum. This area was confirmed by tractography to interconnect somatosensory cortex regions most intensely involved in seizures. This FA decrease was not present in young WAG/Rij rats before onset of SWD. GAERS, which have more severe SWD than WAG/Rij, exhibited even more pronounced callosal FA decreases. Reduced FA in the epileptic animals originated from an increased λ⊥ with no significant changes in λ∥. Interpretation Reduced FA with increased λ⊥ suggests that chronic seizures cause reduction in myelin or decreased axon fiber density in white matter pathways connecting regions of seizure activity. These DTI abnormalities may improve the understanding of chronic neurological difficulties in children suffering with absence epilepsy, and may also serve as a noninvasive biomarker for monitoring beneficial effects of treatment.

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Chronic levetiracetam treatment early in life decreases epileptiform events in young GAERS, but does not prevent the expression of spike and wave discharges during adulthood

Cited by 23 publications

References 29 publications

A New Frontier in Epilepsy: Novel Antiepileptogenic Drugs

A New Frontier in Epilepsy: Novel Antiepileptogenic Drugs

Anticonvulsive and antiepileptogenic effects of levetiracetam in the audiogenic kindling model

DTI abnormalities in anterior corpus callosum of rats with spike–wave epilepsy

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