Changes in Hippocampal Volume are Correlated with Cell Loss but Not with Seizure Frequency in Two Chronic Models of Temporal Lobe Epilepsy

Abstract

Kainic acid (KA) or pilocarpine (PILO) have been used in rats to model human temporal lobe epilepsy (TLE) but the distribution and severity of structural lesions between these two models may differ. Magnetic resonance imaging (MRI) studies have used quantitative measurements of hippocampal T2 (T2HP) relaxation time and volume, but simultaneous comparative results have not been reported yet. The aim of this study was to compare the MRI T2HP and volume with histological data and frequency of seizures in both models. KA- and PILO-treated rats were imaged with a 2 T MRI scanner. T2HP and volume values were correlated with the number of cells, mossy fiber sprouting, and spontaneous recurrent seizures (SRS) frequency over the 9 months following status epilepticus (SE). Compared to controls, KA-treated rats had unaltered T2HP, pronounced reduction in hippocampal volume and concomitant cell reduction in granule cell layer, CA1 and CA3 at 3 months post SE. In contrast, hippocampal volume was unchanged in PILO-treated animals despite detectable increased T2HP and cell loss in granule cell layer, CA1 and CA3. In the following 6 months, MRI hippocampal volume remained stable with increase of T2HP signal in the KA-treated group. The number of CA1 and CA3 cells was smaller than age-matched CTL group. In contrast, PILO group had MRI volumetric reduction accompanied by reduction in the number of CA1 and CA3 cells. In this group, T2HP signal was unaltered at 6 or 9 months after status. Reductions in the number of cells were not progressive in both models. Notably, the SRS frequency was higher in PILO than in the KA model. The volumetry data correlated well with tissue damage in the epileptic brain, suggesting that MRI may be useful for tracking longitudinal hippocampal changes, allowing the assessment of individual variability and disease progression. Our results indicate that the temporal changes in hippocampal morphology are distinct for both models of TLE and that these are not significantly correlated to the frequency of SRS.

Lacosamide modulates interictal spiking and high-frequency oscillations in a model of mesial temporal lobe epilepsy

“…This increase could be explained by the progressive neuronal loss in the hippocampus after SE. Indeed, a reduction of hippocampal volume was found in pilocarpine-treated animals after SE (Nairismagi et al, 2006;Niessen et al, 2005;Polli et al, 2014) and high rates of fast ripples were linked to small hippocampal volumes in epileptic patients (Staba et al, 2007). We also recently found that in CA3, isolated fast ripples, but not fast ripples associated to interictal spikes, occur at high rates during the chronic period (Salami et al, 2014).…”

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

“…Within 48 h after injection and mainly in animals that showed robust convulsions during status epilepticus, there is a loss of pyramidal cells in the CA1, CA3 and CA4 regions of the hippocampus (Ben-Ari et al, 1980;Cantallops and Routtenberg, 2000;Castro-Torres et al, 2014;Drexel et al, 2012;Haas et al, 2001;Heggli and Malthe-Sørenssen, 1982;Kar et al, 1997;MacGregor et al, 1996;Sloviter and Damiano, 1981;Sperk et al, 1983;Strain and Tasker, 1991;Suárez et al, 2012;Zhang et al, 2002). Animals surviving longer time periods (more than 48 h) after status epilepticus show neuron loss in the hilus and cell layer dispersion in the dentate gyrus, mossy fiber sprouting, shrinkage of nerve cells in the piriform and entorhinal cortices, olfactory bulb, substantia nigra, thalamus and mesencephalon (Ben-Ari et al, 1980;Buckmaster and Dudek, 1997;Covolan and Mello, 2000;Polli et al, 2014). Some studies have demonstrated that kainic acid-induced neuronal damage may however be strain-dependent (Cantallops and Routtenberg, 2000).…”

“…Both models are also associated to the occurrence of clusters of seizures. The only main difference relating to the chronic period between the two models is the seizure frequency, since pilocarpine-treated animals show significantly higher seizure rates as compared to kainic acid-treated animals (Polli et al, 2014).…”

Impact of neonatal anoxia on adult rat hippocampal volume, neurogenesis and behavior

“…One author (RSP), blind to the group's identity manually outlined the hippocampus and intracranial vault. For volumetric analyses, the region of interest (ROI) representing the hippocampus was assessed in six regularly separated T2-weighted coronal sections (Figure 1), from 2.1 mm to 6.1 mm caudal to bregma as previously described (Polli, Malheiros et al 2014).…”