Amygdala Kindling in the WAG/Rij Rat Model of Absence Epilepsy

Radboud University Nijmegen, Nymegen, Gelderland, Netherlands
Epilepsia (Impact Factor: 4.57). 02/2006; 47(1):33-40. DOI: 10.1111/j.1528-1167.2006.00367.x
Source: PubMed


The kindling model in rats with genetic absence epilepsy is suitable for studying mechanisms involved in the propagation and generalization of seizure activity in the convulsive and nonconvulsive components of epilepsy. In the present study, we compared the amygdala kindling rate and afterdischarge characteristics of the nonepileptic Wistar control rat with a well-validated model of absence epilepsy, the WAG/Rij rat, and demonstrated the effect of amygdala kindling on spike-and-wave discharges (SWDs) in the WAG/Rij group.
Electrodes were stereotaxically implanted into the basolateral amygdala of rats for stimulation and recording and into the cortex for recording. After a recovery period, the animals were stimulated at their afterdischarge thresholds. EEG was recorded to analyze SWDs and afterdischarge durations. The seizure severity was evaluated by using Racine's 5-stage scale.
All nonepileptic control and four of seven WAG/Rij animals reached a stage 5 seizure state, whereas three animals failed to reach stage 3, 4, or 5 and stayed at stage 2 after application of 30 stimulations. Interestingly, WAG/Rij rats, resistant to kindling, demonstrated a significantly longer duration of SWDs on the first day of the experiment before kindling stimulation than did the kindled WAG/Rij animals. Additionally, the cumulative total duration and the number of SWDs after the kindling stimulation were statistically increased compared with SWDs before kindling stimulation.
The results of our study demonstrate that the progress of amygdala kindling is changed in rats with genetic absence epilepsy, perhaps as a consequence of the hundreds of daily SWDs.

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Available from: Rezzan Gülhan, Oct 10, 2014
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    • "Recent studies have shown that GAERS display a resistance to the secondary generalization of limbic seizures of experimental temporal lobe epilepsy produced by amygdaloid kindling (Es¸kazan et al., 2002). In addition, a sub-group of WAG/Rij has also shown a resistance to amygdaloid kindling, which was correlated with the duration of basal SWDs (Aker et al., 2006; Onat et al., 2007). These experimental results acquire clinical significance by observations that idiopathic generalized absence epilepsy rarely coexists with partial temporal lobe epilepsy (Koutroumanidis et al., 1999; Nicholson et al., 2004). "
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    ABSTRACT: WAG/Rij and GAERS rats show delays or resistance to secondary generalization of limbic seizures during amygdaloid kindling. In this study, we aimed to evaluate the kindling from a different limbic site, hippocampus, and to compare its effects on spike-and-wave discharges (SWDs) with that of amygdaloid kindling. Recording electrodes were implanted epidurally and a stimulation/recording electrode was implanted into the ventral hippocampus in the WAG/Rij, GAERS and Wistar rats. Animals received kindling stimulation twice daily at their afterdischarge thresholds until they reached stage 5 seizures, or the maximum number of stimulations (50) had been delivered. The EEG was recorded to analyze SWDs and afterdischarge durations. All Wistar rats reached stage 5 by the 34th stimulation. 4 of 8 WAG/Rij rats and 3 of 6 GAERS rats displayed stage 4/5 seizures (kindling-prone rats); the rest stayed at stage 2 seizures (kindling-resistant rats) even after 50th stimulations. The cumulative duration and number of SWDs decreased in the post-stimulation period after the first stage 2 seizures, whereas these parameters increased after the first stage 3 seizures in the kindling-prone WAG/Rij and GAERS. The peak frequency of SWDs and its harmonics decreased significantly only in the GAERS group after stage 4 seizures. Hippocampal kindling resembles amygdaloid kindling in showing a delay of or resistance to secondary seizure generalization, which supported the interaction of thalamo-cortical and limbic circuitry in GAERS and WAG/Rij.
    Epilepsy Research 10/2008; 81(2-3):211-9. DOI:10.1016/j.eplepsyres.2008.06.004 · 2.02 Impact Factor
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    • "s a control group . In the present study , kind - ling - resistant rats were found not only in WAG / Rij strain but also among Wistar rats without SWD activity , sug - gesting that absence seizures hardly play a causative role in resistance to kindling . In electrical kindling studies , all Wistar rats were fully kindled ( Eskazan et al . , 2002 ; Aker et al . , 2006 ) . Nevertheless , rapidly and slowly kindled rats of the outbred Wistar strain have been previously described in the electrical kindling model ( Racine et al . , 1999 ) . Thus , the results of the present study do not support the hypothesis about inhibitory role of absence seizures in kindling epileptogenesis . It is more likely that b"
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    ABSTRACT: Audiogenic kindling (AK) is a model of naturally occurring epileptogenesis triggered by repeated sound stimulation of rats genetically prone to audiogenic seizures. It is accepted that limbic seizure networks underlie progressive changes in behavioral seizure pattern during AK. The present study investigated AK progression in rats susceptible and unsusceptible to absence seizures. Progression of AK as indicated by an appearance and intensification of limbic clonus was examined in Wistar Albino Glaxo/Rijswijk (WAG/Rij) rats with genetic absence epilepsy and in Wistar rats. Subpopulations of kindling-prone and kindling-resistant rats were found in both Wistar and WAG/Rij strains. Despite identical seizure responses to the first sound stimulation, AK progression dramatically differed between the two subpopulations. AK-prone rats exhibited rapid kindling development up to maximal stage-5 severity. In AK-resistant rats, limbic clonus did not appear after 30 stimulations or if it appeared, it did not progress beyond stage 2. The proportions of AK-prone and AK-resistant animals within Wistar and WAG/Rij strains were similar. Comparison of Wistar and WAG/Rij rats within the kindling-prone and kindling-resistant groups did not reveal a significant strain effect on AK progression. However, within the WAG/Rij strain, a significantly higher incidence of absence seizures was found in AK-resistant rats compared to AK-prone rats. The present study demonstrates that sensitivity to sound-induced epileptogenesis differs dramatically within Wistar and WAG/Rij strains, whereas genetic susceptibility to absence seizures does not change AK progression significantly. It is supposed that an increased incidence of nonconvulsive seizures and resistance to kindling result from a common seizure modulating mechanism.
    Epilepsia 06/2008; 49(10):1665-74. DOI:10.1111/j.1528-1167.2008.01617.x · 4.57 Impact Factor
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    • "Besides our own data on lower thresholds for limbic type of afterdischarges in WAG/Rij rats [26], Lason et al. found elevated levels of ␣-neoendorphin and up-regulation of the mRNA-encoding prodynorphin in the hippocampus of 6 month old WAG/Rij rats in comparison with younger rats of the same strain and age matched ACI rats [12]. Aker et al. [2] found that WAG/Rij rats but also GAERS are more resistant to amygdala kindling. There are also data found in GAERS indicating that at postnatal day 21 (before the occurrence of SWDs), GAERS have higher brain metabolic activation in limbic regions, but not in the thalamo-cortical loop in comparison to non-epileptic control rats [18]. "
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    ABSTRACT: Classical theories on absence epilepsy suggest that spike-wave discharge (SWDs) represent thalamo-cortical oscillations, where an abnormally excitable cortex interacts with thalamus and brain stem reticular formation. The limbic system is generally not included in any theory about the pathogenesis of absence seizures. However, some data demonstrated that the alterations in the limbic system attribute to the expression of absence epileptic phenotype in genetic models of absence epilepsy. The present study investigated whether local intrahippocampal administration of progesterone (a GABA(A)-mimetic) and tiagabine (an inhibitor of GABA (re)uptake) might affect the occurrence of SWDs. Male WAG/Rij rats were implanted with permanent electroencephalograph (EEG) electrodes and bilateral cannulas in the CA1-CA3 region of the dorsal hippocampus. Control rats had bilateral cannulas in the cortical area above the hippocampus. Rats received intracerebral injections of progesterone (5mg/ml), 45% beta-cyclodextrin (CD), saline, or tiagabine (2mg/ml). EEG recordings were made before and after injection. Progesterone, CD, and tiagabine administration to the hippocampus reduced SWDs for 60min following administration without behavioral or electroencephalographic side-effects. Both progesterone administration into the cortex and saline injection into the hippocampus yielded no changes in the occurrence of SWDs. These data suggest that activation of GABA-ergic transmission in the hippocampus has an inhibitory effect on cortico-thalamo-cortical circuits underlying the generation of SWDs and might be critically involved in the regulation of absence seizures.
    Neuroscience Letters 05/2007; 416(1):17-21. DOI:10.1016/j.neulet.2007.01.038 · 2.03 Impact Factor
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