Effect of Antiepileptic Drugs on Absence‐Like Seizures in the Tremor Rat

Abstract

We examined the effects of conventional antiepileptic drugs (AEDs) on absence-like seizures in homozygous tremor rats (tm/tm) to determine if they corresponded pharmacologically to human absence seizures and absence-like seizures in spontaneously epileptic rats (SER: zi/zi, tm/tm) with both tonic convulsive and absence-like seizures. Cortical and hippocampal EEG activity was recorded with chronically implanted electrodes. The effects of AEDS on seizures of the tremor rat showed profiles similar to those observed in human absence seizures and also in absence-like seizures of SER. The absence-like seizures, associated with paroxysmal bursts of 5-7-Hz spike-wave complexes, were inhibited by trimethadione (TMO 200 mg/kg intraperitoneally, i.p.), ethosuximide (ESM 100 and 200 mg/kg, i.p.), valproate (VPA 100 mg/kg, i.p.), and phenobarbital (PB 10 and 20 mg/kg, i.p.). Phenytoin (PHT 20 mg/kg, i.p.) was ineffective. These results are consistent with the conclusion that the tremor rat is a useful model for evaluating new AEDS for human absence seizures.

Investigating the Role of Zinc in a Rat Model of Epilepsy

“…for 3 weeks before saline injection. normal control rats that received valproic acid (Depakene, Abbott Pharmaceuticals, North Chicago, IL, USA) in 0.9% saline vehicle, in a therapeutic dose of 100 mg/kg bwt daily i.p. [20] for 3 weeks before saline injection. normal control rats that received a combination of valproic acid, in a dose of 100 mg/kg bwt daily i.p. and Zn in a dose of 3 mg/kg bwt for 3 weeks before saline injection. rats in which seizures were induced by i.p.…”

Accumulation of N‐Acetyl‐L‐Aspartate in the Brain of the Tremor Rat, a Mutant Exhibiting Absence‐Like Seizure and Spongiform Degeneration in the Central Nervous System

“…Seizure disorders or epilepsy syndromes are presently classified into Ͼ40 distinct types (Commission on Classification and Terminology of the International League Against Epilepsy, 1989). Although most epilepsies are considered to be multifactorial diseases, some specific types are considered single-gene disorders (Steinlein et al, 1995;Pennacchio et al, 1996;Biervert et al, 1998;Charlier et al, 1998;Fox et al, 1998;Singh et al, 1998;Wallace et al, 1998;McNamara, 1999).The tremor rat is a single-gene mutant found in the Kyoto:Wistar colony that exhibits absence-like seizure characterized by sudden immobility and staring, simultaneously with the appearance of 5-to 7-Hz spike-wave complexes in cortical and hippocampal EEG (Yamada et al, 1985;Serikawa et al, 1987;Hanaya et al, 1995). Homozygous rats (tm/tm) for the causative genetic locus tremor (tm) exhibit absence-like seizure after the age of 14 weeks, whereas heterozygotes (tm/ϩ) exhibit the same seizure less frequently after 26 weeks (Higashiguchi et al, 1991).…”

“…The tremor rat is a single-gene mutant found in the Kyoto:Wistar colony that exhibits absence-like seizure characterized by sudden immobility and staring, simultaneously with the appearance of 5-to 7-Hz spike-wave complexes in cortical and hippocampal EEG (Yamada et al, 1985;Serikawa et al, 1987;Hanaya et al, 1995). Homozygous rats (tm/tm) for the causative genetic locus tremor (tm) exhibit absence-like seizure after the age of 14 weeks, whereas heterozygotes (tm/ϩ) exhibit the same seizure less frequently after 26 weeks (Higashiguchi et al, 1991).…”

Magnetoencephalography localizing spike sources of atypical benign partial epilepsy

“…In 13 (72%) of the 18 ABPE patients studied herein, ESM completely suppressed their ENM. In other studies, systemic administration of ESM significantly reduced spike and wave discharges in genetic absence epilepsy models [17][18][19]. Continuous and generalized slow spike and waves during sleep in patients with ECSWS have been associated with secondary bilateral synchrony with leading foci [20,21].…”

“…The role of MEG remains to be explored in this entity. Kelemen et al [17] reported three patients with CSWS secondary to destructive lesions in the thalamus [14], and CSWS development was often observed in patients with a thalamic lesion, indicative of thalamo-cortical dysfunction with an epileptic 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 Shiraishi et al, page 18 network [15,16]. ESM can be efficacious for seizures In ABPE patients, especially for ENM [6].…”