Status Epilepticus Dynamics Predicts Latency to Spontaneous Seizures in the Kainic Acid Model

Relationship between Delta Rhythm, Seizure Occurrence and Allopregnanolone Hippocampal Levels in Epileptic Rats Exposed to the Rebound Effect

“…A required premise for our experiment was the confirmation of the anticonvulsant effects of LEV. To this aim, we adopted the systemic KA model of chronic epilepsy [17], by introducing substantial differences with respect to most of the published research on testing AEDs in the same animal model. With few exceptions [21], the previous experiments did not address the frequency of nonconvulsive SRSs or the overall seizure duration, but only the frequency of convulsive SRSs was monitored by behavioral analysis [22].…”

“…Particularly, tolerance to LEV could be a result of functional adaptation of LEV's target(s) to the presence of the AED, which might result in increased seizure frequency after AED discontinuation. However, in the attempt to define a risk index for the rebound effect after rapid AED withdrawal, our animal model could be useful [17,18,32], since our animals developed an abrupt increase of generalized tonic-clonic SRSs, after LEV discontinuation. Alternatively, other mechanisms could contribute to the rebound effect, in particular the time window in which specific brain areas might be interested by neurogenesis [33].…”

“…Moreover, the termination of status epilepticus was accompanied by recovery of normal behavior. In our animal model, status epilepticus was allowed to self-terminate [17].…”

“…Seizures were defined as ECoG segments with a minimum duration of 10 s, continuous synchronous high-frequency activity, and an amplitude of at least twice the previous baseline [17]. They were also screened for the presence of a postictal depression, that was the period of time in which the brain recovered from the seizure before regaining normal function.…”

“…LEV has the advantage of being water-soluble and thus can be administered without using any solvent potentially able to affect the central nervous system function. To this regard, LEV appears as an ideal tool to test the rebound effect in a post-status epilepticus model of chronic epilepsy [17]. Thus, we decided to use LEV and designed an experiment to fully characterize its therapeutic properties and the consequences of LEV rapid withdrawal.…”