Pilocarpine Model Of Seizures Research Articles

Antioxidant mechanisms of iso-6-cassine in suppressing seizures induced by pilocarpine

The aim of this study was to evaluate the in vitro antioxidant effects of 12-[(2R,5R,6R)-5-hydroxy-6-methylpiperidin-2-yl]dodecan-2-one (iso-6-cassine; ISO) and the anticonvulsant effects of ISO on pilocarpine-induced seizures in rats. Wistar rats were treated with 0.9% saline (i.p., control group), pilocarpine (400 mg/kg, i.p., pilocarpine group), and the association of ISO (1.0 mg/kg, i.p.) plus pilocarpine (400 mg/kg, i.p.), 30 min after administration of ISO (ISO plus pilocarpine group). After the treatments all groups were observed for 1h. The antioxidant effect of ISO on the pilocarpine model was assessed by determining the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST) and catalase (CAT) as well as the levels of reactive species (RS) and lipid peroxidation (LP). In vitro, ISO (5 μM) reduced RS and LP. ISO (1.0 mg/kg) and abolished seizures and death induced by pilocarpine in rats. ISO protected against the increase in the RS and LP levels, GST activity as well as the inhibition of GPx activity caused by pilocarpine. In addition, ISO increased the catalase activity in hippocampus of seized rats. In conclusion, the dta suggest that ISO can present anticonvulsant and antioxidant properties in the pilocarpine model of seizures in rats.

Evidences for pharmacokinetic interaction of riluzole and topiramate with pilocarpine in pilocarpine-induced seizures in rats

In this study we investigated the effectiveness of two antiepileptic drugs: riluzole and topiramate against pilocarpine-induced seizures, which are considered to be a model of intractable epilepsy commonly used to investigate the antiepileptic effect of drugs and mechanisms of epileptogenesis. Seizures and status epilepticus were induced by pilocarpine in adult male Wistar rats. Riluzole (1-4mg/kg) administered intraperitoneally before pilocarpine dose-dependently protected rats against seizures with the anticonvulsant ED(50) value (50% effective anticonvulsant dose) of 1.8 (1.3-2.6)mg/kg. In contrast, riluzole at 8 and 12mg/kg administered after the onset of pilocarpine-induced seizures affected neither status epilepticus nor mortality of rats. Topiramate significantly enhanced convulsive action of pilocarpine, lowering the convulsant CD(50) value (50% effective convulsant dose) of pilocarpine from 350.8 (329.2-373.8) to 246.4 (218.6-278.2)mg/kg. Riluzole (4mg/kg) lowered plasma and brain concentration of pilocarpine administered at a dose of 400mg/kg from 168.0+/-8.6 to 75.3+/-19.9microg/ml and from 193.7+/-6.6 to 97.0+/-26.1microg/g, respectively. Topiramate (200mg/kg) increased plasma and brain concentration of pilocarpine administered at a dose of 300mg/kg from 78.1+/-2.9 to 106.0+/-6.8microg/ml and from 138.4+/-5.0 to 155.2+/-5.1microg/g, respectively. It seems that both anticonvulsant effect exerted by riluzole and proconvulsant effect exerted by topiramate in pilocarpine model of seizures are due to a pharmacokinetic interaction. Therefore, we postulate that the concentration of pilocarpine should be measured routinely whenever the anticonvulsant effect of drugs is determined in the pilocarpine model of seizures.

Anticonvulsant and antioxidant effects of 3-alkynyl selenophene in 21-day-old rats on pilocarpine model of seizures

This study investigated the anticonvulsant effect of 3-alkynyl selenophene (3-ASP) on pilocarpine (PC)-, pentylenetetrazole (PTZ)- and kainic acid (KA)-induced seizures and mortality in 21-day-old rats. Rats were pretreated by oral route (p.o.) with 3-ASP (10, 25 and 50 mg/kg) before intraperitoneal (i.p.) administration of PC (400 mg/kg), PTZ (80 mg/kg) or KA (45 mg/kg). 3-ASP increased the latency to the seizure onset on PTZ and KA models. At the dose of 50 mg/kg, 3-ASP avoided the death caused by PTZ and KA. 3-ASP (50 mg/kg) abolished seizures and death induced by PC in rats. To investigate the antioxidant effect of 3-ASP on rats exposed to PC, the activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), acetylcholinesterase (AChE), Na +K +ATPase, superoxide dismutase (SOD) and catalase (CAT) as well as the levels of reactive species (RS) and ascorbic acid (AA) were determined in brains of rats. 3-ASP protected against the increase in RS levels and CAT activity induced by PC in brains of rats. The decrease in the levels of AA and inhibition of Na +K +ATPase, SOD and AChE activities caused by PC were protected by 3-ASP. Subeffective doses of 3-ASP plus diazepam, 5S,10R-(+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine maleate (MK-801) or 6,7-dinitroquinoxaline-2,3-dione (DNQX) increased the latency to the seizure onset induced by PC, suggesting the involvement of ionotropic glutamatergic and GABAergic receptors in anticonvulsant action of 3-ASP. The anticonvulsant and antioxidant effects of 3-ASP in 21-day-old rats on PC model were demonstrated.

Tonic–clonic seizures induce division of neuronal progenitor cells with concomitant changes in expression of neurotrophic factors in the brain of pilocarpine–treated mice

Epileptic seizures cause severe and long-lasting events on the architecture of the brain, including neuronal cell death, accompanied neurogenesis, reactive gliosis, and mossy fiber sprouting. However, it remains uncertain whether these functional and anatomical alterations are associated with the development of hyperexcitability, or as inhibitory processes. Neurotrophic factors are probable mediators of these pathophysiological events. The present study was designed to clarify the role of various neurotrophic factors on the pilocarpine model of seizures. At 4 h following pilocarpine-induced seizures, expression of NGF, BDNF, HB-EGF, and FGF-2 increased only in the mice manifesting tonic–clonic convulsions and not in mice without seizures. NT-3 expression decreased in pilocarpine-treated mice experiencing seizures, tonic–clonic or not, compared to mice with no seizures. Neuronal cell damage, which was evident by Fluoro-Jade B staining, was observed within 24 h in the mice exhibiting tonic–clonic seizures, followed by an increase in the number of BrdU-positive cells and glial cells, which were evident after 2 days. None of these pathophysiological changes occurred in the mice which showed no seizures, although they were injected with pilocarpine, nor in the activated epilepsy-prone EL mice, which experienced repeated severe seizures. Together, these results suggest that neuronal damage occurring in the brain of the mice manifesting tonic–clonic seizures is accompanied by neurogenesis. This sequence of events may be regulated through changes in expression of neurotrophic factors such as NGF, BDNF, HB-FGF, and NT-3.