Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in rat

Abstract

Pilocarpine administration to rats results in status epilepticus (SE) and after a latency period to the occurrence of spontaneous seizures. The model is commonly used to investigate mechanisms of epileptogenesis as well as the antiepileptic effects of novel compounds. Surprisingly, there have been no video-EEG studies determining the duration of latency period from SE to the appearance of the first spontaneous seizures or the type and frequency of spontaneous seizures at early phase of pilocarpine-induced epilepsy even though such information is critical for design of such studies. To address these questions, we induced SE with pilocarpine in 29 adult male Wistar rats with cortical electrodes. Rats were continuously video-EEG monitored during SE and up to 23 days thereafter. The first spontaneous seizures occurred 7.2+/-3.6 days after SE. During the follow-up, the mean daily seizure frequency was 2.6+/-1.9, the mean seizure duration 47+/-7 s, and the mean behavioral seizure score 3.2+/-0.9. Typically first seizures were partial (score 1-2). Interestingly, spontaneous seizures occurred in clusters with cyclicity, peaking every 5 to 8 days. These data show that in the pilocarpine model of temporal lobe epilepsy the latency period is short. Because many of the early seizures are partial and the seizures occur in clusters, the true phenotype of epilepsy triggered by pilocarpine-induced SE may be difficult to characterize without continuous long-term video-EEG monitoring. Finally, our data suggest that the model can be used for studies aiming at identifying the mechanisms of seizure clustering.

Long-term decrease in calbindin-D28K expression in the hippocampus of epileptic rats following pilocarpine-induced status epilepticus

“…Although these seizure frequencies are only estimates of the actual seizure frequency over long time periods, they are comparable with the observations from other major laboratories using the pilocarpine model of AE: Pitkanen and co-workers have reported a frequency of 2.6 seizures per day (Goffin et al, 2007); Holmes and co-workers have reported 5.2 seizures per 42 h (Cha et al, 2004), and Dudek and coworkers have reported 6.9 seizures per day (Hernandez et al, 2002). Seizure durations are relatively short (35-50 s) in the pilocarpine model and animals have been shown to tolerate several brief seizures per day without significant behavioral effects (Goffin et al, 2007). Since the seizure frequencies observed in this study were comparable to those described by other laboratories, the observed decrease in calbindin expression presented here in the epileptic animals was not due to a high seizure frequency.…”

“…One animal demonstrated a cluster of high seizure frequencies and skewed the data to reflect a higher mean seizure frequency for this group. For long-term studies, animals were monitored two times at 12 and 24 months following SE and were found to have a mean seizure frequency of 0.9 ± 0.4 seizures per 6 h. The seizure frequencies observed in this study were comparable to those seen in other studies employing the pilocarpine model (Goffin et al, 2007;Hernandez et al, 2002;Cha et al, 2004;Wallace et al, 2003).…”

“…It has been documented that it is difficult to obtain accurate seizure frequency on epileptic rats with monitoring techniques that observe animals for only a few days and some studies monitor continuously while others only monitor for short durations each day (Goffin et al, 2007). In addition, the pilocarpine model of AE manifests a high variability of seizure frequencies between individual rats and studies have demonstrated epileptic rats experiencing clusters of very high seizure frequency contributing to this variability (Mello et al, 1993;Goffin et al, 2007).…”

“…In addition, the pilocarpine model of AE manifests a high variability of seizure frequencies between individual rats and studies have demonstrated epileptic rats experiencing clusters of very high seizure frequency contributing to this variability (Mello et al, 1993;Goffin et al, 2007). Mello et al (1993) demonstrated that some rats had as many as six seizures in an 8 h time.…”

Initiation, Propagation, and Termination of Partial (Focal) Seizures

“…Evolving patterns are commonly observed in posttraumatic and poststroke epilepsy models (Pitkänen et al 2006;Kadam et al 2010), in models of mesial TLE either secondary to pharmacologically induced status epilepticus (Williams et al 2009;Bortel et al 2010;Levesque et al 2012), or induced by kindling (Michalakis et al 1998). As in humans, seizures in experimental animals with partial epilepsy occur randomly, often in clusters (Grabenstatter et al 2005;Goffin et al 2007;Williams et al 2009). In in vitro preparations (brain slices and in toto preparations) isolated from chronically epileptic animals, interictal activity can be seen, but seizures do not occur spontaneously and are usually evoked by either pharmacological manipulations or patterned stimulations.…”