Audiogenic kindling in Wistar and WAG/Rij rats: Kindling‐prone and kindling‐resistant subpopulations

Abstract

SUMMARYPurpose: 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. Methods: 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. Results: 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 kindlingprone 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. Conclusions: 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.

Audiogenic kindling and secondary subcortico-cortical epileptogenesis: Behavioral correlates and electrographic features

“…This idea has been supported by the results of our experiments showing that the repetition of only running episodes (minimal AS) may be sufficient to produce audiogenic kindling [12,33,45].…”

“…1C) [33,45]. The data indicate that audiogenic kindling produced by a severe tonic form of AS (with ventroflexion and full limb extension) elicits PTC while the repetition of submaximal AS (running with or without generalized clonic or clonic-tonic convulsions with back arching tonus) triggers limbic clonus.…”

“…3). These rats with low AS susceptibility exhibit variable responses to repeated sound stimulation and different propensity to kindling epileptogenesis, despite identical patterns of seizures acutely induced by sound [33]. Animals prone and resistant to kindling as well as rats losing AS susceptibility with repeated stimulation have been described among Wistar and WAG/Rij rats.…”

“…However, results of our last experiments showing close association of the running behavior with epileptiform abnormalities in the IC [Vinogradova, Grinenko, unpublished data] suggest that this brief episode of mild running is a part of audiogenic seizure progression that reflects the earliest excitation of the IC induced by sound. Using brief acoustic stimulation of rats with low AS susceptibility, only the earliest episode of running (a focal brainstem seizure) can be induced [12,33,45].…”

“…We developed a protocol of seizure induction by short sound stimulation interrupted with the onset of the initial running behavior [12,33]. Such stimulus only triggers a seizure while subsequent progression of the seizure occurs in the absence of epileptogenic stimulation.…”