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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    • "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). "

    Cognitive Neurodynamics 11/2015; DOI:10.1007/s11571-015-9361-1 · 1.67 Impact Factor
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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.
    Epilepsy & Behavior 09/2015; 52(Pt A):78-92. DOI:10.1016/j.yebeh.2015.08.037 · 2.26 Impact Factor
    • "In comparison to the repeated low dose KA-injection protocol , systemic pilocarpine induced SE has a higher mortality rate of 30–50% (Curia et al., 2008), and mortality rate in the stimulation SE models is comparable with our observations. All rats we injected with KA developed a self-sustained SE consistent with reports on the intrahippocampal KA model (Raedt et al., 2009). "
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    ABSTRACT: Animal models reproducing the characteristics of human epilepsy are essential for the elucidation of the pathophysiological mechanisms. In epilepsy research there is ongoing debate on whether the epileptogenic process is a continuous process rather than a step function. The aim of this study was to assess progression of epileptogenesis over the long term and to evaluate possible correlations between SE duration and severity with the disease progression in the kainic acid model. Rats received repeated KA injections (5mg/kg) until a self-sustained SE was elicited. Continuous depth EEG recording started before KA injection and continued for 30 weeks. Mean seizure rate progression could be expressed as a sigmoid function and increased from 1±0.2 seizures per day during the second week after SE to 24.4±6,4 seizures per day during week 30. Seizure rate progressed to a plateau phase 122±9 days after SE. However, the individual seizure rate during this plateau phase varied between 14.5 seizures and 48.6 seizures per day. A circadian rhythm in seizure occurrence was observed in all rats. Histological characterization of damage to the dentate gyrus in the KA treated rats confirmed the presence of astrogliosis and aberrant mossy fiber sprouting in the dentate gyrus. This long-term EEG monitoring study confirms that epileptogenesis is a continuous process rather than a step function.
    Brain research 09/2015; DOI:10.1016/j.brainres.2015.08.016 · 2.84 Impact Factor
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