The pilocarpine model of temporal lobe epilepsy

Montreal Neurological Institute and Departments of Neurology & Neurosurgery and Physiology, McGill University, Montreal, QC, Canada.
Journal of Neuroscience Methods (Impact Factor: 2.05). 08/2008; 172(2):143-57. DOI: 10.1016/j.jneumeth.2008.04.019
Source: PubMed


Understanding the pathophysiogenesis of temporal lobe epilepsy (TLE) largely rests on the use of models of status epilepticus (SE), as in the case of the pilocarpine model. The main features of TLE are: (i) epileptic foci in the limbic system; (ii) an "initial precipitating injury"; (iii) the so-called "latent period"; and (iv) the presence of hippocampal sclerosis leading to reorganization of neuronal networks. Many of these characteristics can be reproduced in rodents by systemic injection of pilocarpine; in this animal model, SE is followed by a latent period and later by the appearance of spontaneous recurrent seizures (SRSs). These processes are, however, influenced by experimental conditions such as rodent species, strain, gender, age, doses and routes of pilocarpine administration, as well as combinations with other drugs administered before and/or after SE. In the attempt to limit these sources of variability, we evaluated the methodological procedures used by several investigators in the pilocarpine model; in particular, we have focused on the behavioural, electrophysiological and histopathological findings obtained with different protocols. We addressed the various experimental approaches published to date, by comparing mortality rates, onset of SRSs, neuronal damage, and network reorganization. Based on the evidence reviewed here, we propose that the pilocarpine model can be a valuable tool to investigate the mechanisms involved in TLE, and even more so when standardized to reduce mortality at the time of pilocarpine injection, differences in latent period duration, variability in the lesion extent, and SRS frequency.

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Available from: Giulia Curia
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    • "Pilocarpine - Induced SE Mouse to Study Anatomical Changes in Different Brain Regions in Epilepsy Pilocarpine - induced SE , when not interrupted by drug administration , is able to induce reorganization and anatomical damage in brain regions such as the olfactory cortex , amygdala , thalamus , hippocampus and neocortex ( Curia et al . , 2008 ; Reddy and Kuruba , 2013 ) . Pharmacological intervention , such as diazepam , has been used to limit the SE duration to reduce mortality as well as to confine neuronal damage to the hippocampal formation and related limbic regions . One study showed Fluorojade - positive neurodegeneration in near 30 brain regions with several of these"
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    ABSTRACT: In this study, we investigated the reorganized basolateral amygdala (BLA)-subiculum pathway in a status epilepticus (SE) mouse model with epileptic episodes induced by pilocarpine. We have previously observed a dramatic loss of neurons in the CA1–3 fields of the hippocampus in epileptic mice. Herein, we observed a 43–57% reduction in the number of neurons in the BLA of epileptic mice. However, injection of an anterograde tracer, Phaseolus vulgaris leucoagglutinin (PHA-L) into the BLA indicated 25.63% increase in the number of PHA-L-immunopositive terminal-like structures in the ventral subiculum (v-Sub) of epileptic mice as compared to control mice. These data suggest that the projections from the basal nucleus at BLA to the vSub in epileptic mice are resistant to epilepsy-induced damage. Consequently, these epileptic mice exhibit partially impairment but not total loss of context-dependent fear memory. Epileptic mice also show increased c-Fos expression in the BLA and vSub when subjected to contextual memory test, suggesting the participation of these two brain areas in foot shock-dependent fear conditioning. These results indicate the presence of functional neural connections between the BLA-vSub regions that participate in learning and memory in epileptic mice.
    Full-text · Article · Jan 2016 · Frontiers in Neuroanatomy
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    • "Such epileptic animal model thus has been widely used to explore the mechanisms of TLE (Turski et al. 1983). After 1–2 days of pilocarpine-induced status epilepticus (SE), the rats enter a seizure-free period, known as the latent period, and then progressively develop a chronic epileptic condition after weeks (Curia et al. 2008). Classical tests have demonstrated hippocampus-dependent spatial memory deficits during the latent period in pilocarpine-treated rats (Faure et al. 2013; Chauvière et al. 2009). "
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    ABSTRACT: Patients with temporal lobe epilepsy (TLE) often display cognitive deficits. However, current epilepsy therapeutic interventions mainly aim at how to reduce the frequency and degree of epileptic seizures. Recovery of cognitive impairment is not attended enough, resulting in the lack of effective approaches in this respect. In the pilocarpine-induced temporal lobe epilepsy rat model, memory impairment has been classically reported. Here we evaluated spatial cognition changes at different epileptogenesis stages in rats of this model and explored the effects of long-term Mozart music exposure on the recovery of cognitive ability. Our results showed that pilocarpine rats suffered persisting cognitive impairment during epileptogenesis. Interestingly, we found that Mozart music exposure can significantly enhance cognitive ability in epileptic rats, and music intervention may be more effective for improving cognitive function during the early stages after Status epilepticus. These findings strongly suggest that Mozart music may help to promote the recovery of cognitive damage due to seizure activities, which provides a novel intervention strategy to diminish cognitive deficits in TLE patients.
    Full-text · Article · Nov 2015 · Cognitive Neurodynamics
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    • "For instance, for the widely used pilocarpine model, latent periods ranging from 1 to 6 weeks have been reported by using noncontinuous video monitoring or visual observation of seizures [25]. In patients developing epilepsy after brain insults, estimation of latent periods was initially based on anecdotal accounts of retrospective assessment of the time elapsing between a presumed injury and the emergence of unprovoked clinical seizures, resulting in latent periods, if any, that can range from days to months and several years, possibly depending on the severity or nature of the process [26] [27] [28] [29] [30]. "
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    ABSTRACT: A widely accepted hypothesis holds that there is a seizure-free, pre-epileptic state, termed the "latent period", between a brain insult, such as traumatic brain injury or stroke, and the onset of symptomatic epilepsy, during which a cascade of structural, molecular, and functional alterations gradually mediates the process of epileptogenesis. This review, based on recent data from both animal models and patients with different types of brain injury, proposes that epileptogenesis and often subclinical epilepsy can start immediately after brain injury without any appreciable latent period. Even though the latent period has traditionally been the cornerstone concept representing epileptogenesis, we suggest that the evidence for the existence of a latent period is spotty both for animal models and human epilepsy. Knowing whether a latent period exists or not is important for our understanding of epileptogenesis and for the discovery and the trial design of antiepileptogenic agents. The development of antiepileptogenic treatments to prevent epilepsy in patients at risk from a brain insult is a major unmet clinical need.
    Full-text · Article · Sep 2015 · Epilepsy & Behavior
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