Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate

Perez-Mendes, Patrícia; Blanco, Miriam Marcela; Calcagnotto, María Elisa; Cinini, Simone M.; Bachiega, João C.; Papoti, Daniel; Covolan, Luciene; Tannús, Alberto; Mello, Luiz E.

doi:10.1016/j.eplepsyres.2011.04.015

Cited by 30 publications

(18 citation statements)

References 60 publications

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“…Non-human primate models are actually being developed in some laboratories and they appear to be associated to lesions highly similar to what is observed in humans (Perez-Mendes et al, 2011;Zini et al, 1993). More studies comparing the activity and physiological alterations in epileptic human and animal tissues are however needed in order to further establish the validity of these models.…”

Section: Discussionmentioning

confidence: 85%

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Lévesque

Avoli

Bernard

2016

Journal of Neuroscience Methods

210

182

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In order to understand the pathophysiology of temporal lobe epilepsy (TLE), and thus to develop new pharmacological treatments, in vivo animal models that present features similar to those seen in TLE patients have been developed during the last four decades. Some of these models are based on the systemic administration of chemoconvulsants to induce an initial precipitating injury (status epilepticus) that is followed by the appearance of recurrent seizures originating from limbic structures. In this paper we will review two chemically-induced TLE models, namely the kainic acid and pilocarpine models, which have been widely employed in basic epilepsy research. Specifically, we will take into consideration their behavioral, electroencephalographic and neuropathologic features. We will also evaluate the response of these models to anti-epileptic drugs and the impact they might have in developing new treatments for TLE.

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Section: Discussionmentioning

confidence: 85%

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Lévesque

Avoli

Bernard

2016

Journal of Neuroscience Methods

210

182

View full text Add to dashboard Cite

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“…This contrasts significantly with the more restricted damage seen in human TLE patients (Engel, 1996). The injection of pilocarpine in marmosets (Perez-Mendes et al, 2011) has recently been shown to result in more restricted neurodegeneration, ressembling the human pathology, with neuronal damage and abnormal plasticity mainly restricted to the limbic system, particularly the hippocampus (Perez-Mendes et al, 2011). Here we examined the effect of carbamazepine (CBZ), phenobarbital (PB) and valproic acid (VPA), three clinically relevant and widely used AED, in a nonhuman primate model where predictable acutely elicited seizures (by means of PTZ) were generated in an epileptic brain (yielded epileptic by means of SE induction with pilocarpine).…”

Section: Introductionmentioning

confidence: 85%

“…SE induced by pilocarpine SE was induced as described elsewhere (Perez-Mendes et al, 2011). In brief, scopolamine methyl bromide (1 mg/kg, i.p.)…”

Section: Electrode Implantation and Electrocorticography Analysismentioning

confidence: 99%

Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment

et al. 2016

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a b s t r a c tThe efficiency of most of the new antiepileptic drugs (AEDs) on clinical trials still falls short the success reported in pre-clinical studies, possibly because the validity of the animal models is insufficient to fully represent the human pathology. To improve the translational value for testing AEDs, we propose the use of non-human primates. Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED. Marmosets with epileptic background were more susceptible to seizures induced by PTZ, which were at least 3 times longer and more severe (about 6 times greater frequency of generalized seizures) in comparison to naïve peers. Accordingly, PTZ-induced seizures were remarkably less attenuated by AEDs in epileptic than naïve marmosets. While phenobarbital (40 mg/kg) virtually abolished seizures regardless of the animal's background, carbamazepine (120 mg/kg) and valproic acid (400 mg/kg) could not prevent PTZinduced seizures in epileptic animals with the same efficiency as observed in naïve peers. VPA was less effective regarding the duration of individual seizures in epileptic animals, as assessed in ECoG (p = 0.05). Similarly following CBZ treatment, the behavioral manifestation of generalized seizures lasted longer in epileptic (p < 0.05), which were also more frequent than in the naïve group (p < 0.05). As expected, epileptic marmosets experiencing stronger seizures showed more NPY-and FosB-immunostained neurons in a number of brain areas associated with the generation and spread of limbic seizures. Our results suggest that PTZ induced seizures over an already existing epileptic background constitutes a reliable and controllable mean for the screening of new AEDs.

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“…The comparative histopathology after SE indicates that the KA group is more likely to develop and to survive SE, while the PILO group shows a greater number of brain areas affected at a high intensity within a shorter time interval (6). In preclinical models of epilepsy, volumetric magnetic resonance imaging (MRI) studies have shown a significant atrophy of limbic structures as well as T 2 changes that correlate with pathological states (10–16). However, there are no reports comparing the long-term temporal changes that occur in the hippocampus after injections of KA with those after injections of PILO.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2014

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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.

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Modeling epileptogenesis and temporal lobe epilepsy in a non-human primate

Cited by 30 publications

References 60 publications

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Animal models of temporal lobe epilepsy following systemic chemoconvulsant administration

Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment

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

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