Behavioral characteristics as potential biomarkers of the development and phenotype of epilepsy in a rat model of temporal lobe epilepsy

Abstract

The present study performed a detailed analysis of behavior in a rat model of epilepsy using both established and novel methodologies to identify behavioral impairments that may differentiate between animals with a short versus long latency to spontaneous seizures and animals with a low versus high number of seizures. Temporal lobe epilepsy was induced by electrical stimulation of the amygdala. Rats were stimulated for 25 min with 100-ms trains of 1-ms biphasic square-wave pluses that were delivered every 0.5 s. Electroencephalographic recordings were performed to classify rats into groups with a short latency (< 20 days, n = 7) and long latency (> 20 days, n = 8) to the first spontaneous seizure and into groups with a low number of seizures (62 ± 64.5, n = 8) and high number of seizures (456 ± 185, n = 7). To examine behavioral impairments, we applied the following behavioral tests during early and late stages of epilepsy: behavioral hyperexcitability, open field, novel object exploration, elevated plus maze, and Morris water maze. No differences in stress levels (e.g., touch response in the behavioral hyperexcitability test), activity (e.g., number of entries into the open arms of the elevated plus maze), or learning (e.g., latency to find the platform in the Morris water maze test during training days) were observed between animals with a short versus long latency to develop spontaneous seizures or between animals with a low versus high number of seizures. However, we found a higher motor activity measured by higher number of entries into the closed arms of the elevated plus maze at week 26 post-stimulation in animals with a high number of seizures compared with animals with a low number of seizures. The analysis of the Morris water maze data categorized the strategies that the animals used to locate the platform showing that the intensity of epilepsy and duration of epileptogenesis influenced swimming strategies. These findings indicate that behavioral impairments were relatively mild in the present model, but some learning strategies may be useful biomarkers in preclinical studies.

Induction of the Nrf2 Pathway by Sulforaphane Is Neuroprotective in a Rat Temporal Lobe Epilepsy Model

“…Acquired epilepsy, which constitutes up to 50% of all epilepsy cases, is initiated by neurological insults, such as stroke, traumatic brain injury (TBI), and status epilepticus (SE) [ 4 ]. The initial insult is followed by a latency period referred to as epileptogenesis, a progressive activity initiated in the brain following insults or injury, which results into a dynamic sequence of events, including numerous structural, cellular, and molecular changes occurring over time, with a reactive response that generates abnormal patterns of electrical discharges in discrete brain regions resulting in the eventual development of epilepsy, where the brain is capable of generating spontaneous seizures [ 5 , 6 ].…”

Low-dose 7,8-Dihydroxyflavone Administration After Status Epilepticus Prevents Epilepsy Development

“…However, these effects were partial for anxiety, because only a few parameters of the OF were corrected, and all appeared only in the late, chronic phase of the disease, while anxiety traits and cognitive impairments were observed in all animals (including those treated with low-dose 7,8-DHF) in the early phase, i.e., at the time when vehicle-treated animals begin experiencing SRSs. Several behavioral alterations have been observed to follow epileptogenic insults (SE or traumatic brain injury, TBI) in animal models, but the majority of these alterations cannot predict which animals will subsequently become epileptic (i.e., will display SRSs) and which will not [ 42 – 45 ]. In the chronic course of epilepsy, these behavioral alterations are generally maintained [ 43 – 45 ], and this was the case also in the present study.…”

“…Several behavioral alterations have been observed to follow epileptogenic insults (SE or traumatic brain injury, TBI) in animal models, but the majority of these alterations cannot predict which animals will subsequently become epileptic (i.e., will display SRSs) and which will not [ 42 – 45 ]. In the chronic course of epilepsy, these behavioral alterations are generally maintained [ 43 – 45 ], and this was the case also in the present study. Therefore, the observation that animals treated with low-dose 7,8-DHF had improvements at late time points may be attributed to the fact that they did not (or very marginally did) experience SRSs.…”

Strategies discovery in the active allothetic place avoidance task

“…Will we observe the same trajectory classes in other AAPA experiments, depending on the treatments and with other strains? Our earlier work on MWM and the strategies identified therein were in fact used to analyse data from different experiments and labs 24 , 29 , 30 , suggesting that it might be possible that the same generality holds for the AAPAT. However, we need to highlight a fundamental difference.…”