Abstract
Pilocarpine-induced seizures in rats provide a widely animal model of temporal lobe epilepsy. Some evidences reported in the literature suggest that at least 1 h of status epilepticus (SE) is required to produce subsequent chronic phase, due to the SE-related acute neuronal damage. However, recent data seems to indicate that neuro-inflammation plays a crucial role in epileptogenesis, modulating secondarily a neuronal insult. For this reason, we decided to test the following hypotheses: a) whether pilocarpine-injected rats that did not develop SE can exhibit long-term chronic spontaneous recurrent seizures (SRS) and b) whether acute neurodegeneration is mandatory to obtain chronic epilepsy. Therefore, we compared animals injected with the same dose of pilocarpine that developed or did not SE, and saline treated rats. We used telemetric acquisition of EEG as long-term monitoring system to evaluate the occurrence of seizures in non-SE pilocarpineinjected animals. Furthermore, histology and MRI analysis were applied in order to detect neuronal injury and neuropathological signs. Our observations indicate that non-SE rats exhibit SRS almost 8 (+/22) months after pilocarpine-injection, independently to the absence of initial acute neuronal injury. This is the first time reported that pilocarpine injected rats without developing SE, can experience SRS after a long latency period resembling human pathology. Thus, we strongly emphasize the important meaning of including these animals to model human epileptogenesis in pilocarpine induced epilepsy.
Highlights
Temporal lobe epilepsy (TLE) is the most common epileptic syndrome in adult humans; for this reason, the neurobiological bases of TLE have been extensively studied in preclinical research, and adequate animal models paralleling human pathology are required
Control rats did not show any seizure during all the evaluated registration time, and on the other hand, since the first evaluation, pilocarpinetreated animals that develop status epilepticus (SE) (PILOSE animals) developed SRS that were always present until the end of the registration
On the contrary, surprising findings were evidenced in pilocarpine-treated animals that did not develop SE (PILOnoSE animals), in which SRS occurred after eight months (+/22 months) of monitoring EEG and persisted during the whole registration less frequently (0.5–1 seizures/week) than the cyclical pattern observed in pilocarpine injected animals were subdivided in SE (PILOSE) animals (4–6 seizures/week)
Summary
Temporal lobe epilepsy (TLE) is the most common epileptic syndrome in adult humans (see, for review, [1]); for this reason, the neurobiological bases of TLE have been extensively studied in preclinical research (see, i.a., [1,2]), and adequate animal models paralleling human pathology are required. Pilocarpine has been recently used to model pharmacoresistance in TLE [4] This model has been proposed as sufficiently isomorphic with the human disease [5], but several aspects seem to differ significantly, at least concerning the extent of damage and the incidence of SE, as well as the inflammatory origin [6]. 2/3 of human patients suffering TLE presents hippocampal sclerosis, whereas the remaining 1/3 presents focal limbic lesions. This latter group does not exhibit pronounced segmental neuronal cell loss or concomitant sclerosis [7]. The pattern of the damaged structures is similar in both models, but with different temporal profile of brain injury [9]
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