Evaluation of behavioral parameters and mortality in a model of temporal lobe epilepsy induced by intracerebroventricular pilocarpine administration

Abstract

The pilocarpine model of temporal lobe epilepsy (TLE) is a useful tool that is used to investigate the mechanisms underlying the generation and maintenance of seizures. Although this model has been modified significantly to reduce mortality and to promote the appearance of spontaneous recurrent seizures, to date, no detailed evaluation has been performed of the behavioral parameters and mortality in TLE induced by intracerebroventricular pilocarpine administration; therefore, this was the goal of the present study. A single dose of pilocarpine hydrochloride (2.4 mg in a total volume of 2 µl) was injected into the right lateral brain ventricle of rats; the convulsive behavior was rated using the Racine scale and the mortality was analyzed in these animals. We found that 30-90 min after animals received intracerebroventricular pilocarpine injections, 73% developed status epilepticus (SE) with an activity score of 4/5 on the Racine scale. Moreover, these seizures were associated with the propagation of epileptiform activity to different hippocampal regions. Of the animals that developed SE, spontaneous recurrent seizures were observed in 32.5% at different times after SE induction. A 35% mortality rate was observed, which included animals that died during pilocarpine injection and after SE induction. On the basis of these findings, and given the observed latency between the insult (SE induction by pilocarpine injection) and the manifestation of spontaneous recurrent seizures, we propose that this model is a useful tool for basic biomedical research of SE and TLE.

Serotonin modulates fast ripple activity in rats with spontaneous recurrent seizures

“…The convulsive behavior of all the animals after pilocarpine injection was monitored visually, and 15 days after SE induction the rats were monitored on video for 24 h for two or three weeks every month and their spontaneous recurrent seizures scored. Animals exhibiting spontaneous recurrent seizures were selected for microelectrode implantation (Medina-Ceja et al, 2014).…”

Chemically-induced TLE models: Topical application

“…In addition to the more restricted damage, they also reported lower mortality, higher reliability to induce SE, and faster recovery from SE after focal injection of pilocarpine . After intracerebroventricular injection of pilocarpine (2.4 mg in 2 l), mortality was higher (35%) and only 32.5% of the animals developed SRS (Medina-Ceja et al, 2014). Together, unilateral intrahippocampal injection of pilocarpine offers a reasonable model of TLE, with lower mortality and a more restricted pattern of neuronal damage compared with systemic application.…”

“…Pilocarpine has been shown to trigger acute and chronic seizures after intracerebroventricular and intrahippocampal administration (Croiset and De, 1992;Millan et al, 1993;Smolders et al, 1997;Lindekens et al, 2000;Furtado et al, 2002Furtado et al, , 2011Castro et al, 2011;Medina-Ceja et al, 2014). Detailed behavioral, electrophysiological and morphological analyses have been performed in mice by Furtado et al (2002Furtado et al ( , 2011.…”

A novel method for simultaneous glutamate and extracellular activity measurement in brain slices with high temporal resolution

“…The electrodes were then connected to this module. The analog signal was converted to a digital signal with a MP150 data acquisition module from BIOPAC at 5 kHz, and the data were To obtain epileptic rats we used the pilocarpine model [27]. Briefly, the animals were anesthetized with isoflurane (Sofloran, PISA Laboratories, Mexico) in 100% oxygen and secured in a Stoelting stereotaxic frame with the incisor bar positioned at -3.3 mm.…”