Variable electrobehavioral patterns during focal nonconvulsive status epilepticus induced by unilateral intrahippocampal injection of kainic acid

Abstract

SUMMARYObjective: Nonconvulsive status epilepticus (ncSE) is a severe condition that may result in neurologic sequelae and epilepsy resistant to pharmacologic treatment. We analyze here seizure and electroencephalography (EEG) patterns and their correlation to the development of a chronic epileptic condition in a guinea pig model of focal ncSE induced by intrahippocampal injection of kainic acid (KA). Methods: Electrobehavioral patterns during ncSE induced by unilateral injection of 1 lg of KA in the CA1 region of the hippocampus were characterized by continuous video-EEG monitoring in 13 guinea pigs bilaterally implanted with recording electrodes in the hippocampus and neocortex. Results: Video-EEG analysis demonstrates a high variability of seizure type and duration during KA-induced ncSE. Seizures showed focal signs correlated with diverse epileptiform EEG discharge distributions, either diffuse or localized. Nonfocal (bilateral motor) signs during seizures most likely correlated with a diffuse EEG pattern. The evolution into a chronic epileptic condition correlated neither with the severity of seizure pattern nor with the diffusion of the EEG discharges observed during the ncSE. Significance: Video-EEG monitoring in a guinea pig model of ncSE induced by unilateral hippocampal injection of KA demonstrates a high variability of electrobehavioral patterns. We demonstrate that the seizure severity score during focal ncSE is not a predictor of the evolution into a chronic epileptic condition of mesial temporal lobe epilepsy.

Epileptiform activity contralateral to unilateral hippocampal sclerosis does not cause the expression of brain damage markers

“…12,13 Surgeries, animal shuffle in the different experimental groups, and intrahippocampal injections were performed by Fraqncesco Noè (acute ncSE) and Alessandro Cattalini (chronic mTLE animals). A 30-gauge needle, connected to a 5 μL Hamilton syringe via a polyethylene tube, was lowered through the guide cannula in the right hippocampus to slowly inject 1 μL of 1 μg KA (Sigma) diluted in 0.9% NaCl solution.…”

“…Hippocampal EEG patterns during and after KA injection were identified and quantified for each animal. 13 Extracellular population spike number and distribution ( Figure 2) were quantified in both hippocampi by setting a threshold 2.5 standard deviations above the baseline amplitude, as calculated on the pre-KA injection EEG recording. KA-induced epileptiform activity was characterized by seizures combined with continuous rhythmic spiking activity at 1-3 Hz ( Figure 1).…”

“…3,5 Because seizure frequency usually intensifies in parallel with brain injury worsening, it has been suggested that seizure activity by itself may have a direct pathogenic action on tissue reorganization and may possibly worsen brain damage. To this end, we utilized a guinea pig model of unilateral mTLE 12,13 induced by local injection in one hippocampus of kainic acid (KA), [14][15][16] a neurotoxin known to induce within 24 hours an acute calcium-dependent neurodegeneration. Brain injury progression has been documented during the life span of animals that develop mesial temporal lobe epilepsy (mTLE) with hippocampal sclerosis as consequence of SE, 7-10 and after brain concussion.…”

The in vitro isolated whole guinea pig brain as a model to study epileptiform activity patterns

“…Advantages and disadvantages of the in vitro IWB in comparison to other in vitro models and to the in vivo condition are summarized in Table 1. As future advancement, we plan to isolate brains from chronically epileptic guinea pigs (Arcieri et al, 2014;Carriero et al, 2012) to study network changes induced by the epileptogenic process.…”

Status Epilepticus

“…Models of nonconvulsive SE (NCSE) are limited (Krsek et al 2001;Wong et al 2003;Arcieri et al 2014), and none of the currently available models replicate the key components of the form of NCSE that occurs in the ICU setting. SE can be induced using hyperthermia in young rats and mice; however, to date, this "febrile SE" model has been primarily used to study the epileptogenic process and not SE per se (Dube et al 2010;Patterson et al 2014).…”