Anticonvulsant Effects of Topiramate and Lacosamide on Pilocarpine-Induced Status Epilepticus in Rats: A Role of Reactive Oxygen Species and Inflammation

Abstract

Background: Status epilepticus (SE) is a neurological disorder characterized by a prolonged epileptic activity followed by subsequent epileptogenic processes. The aim of the present study was to evaluate the early effects of topiramate (TPM) and lacosamide (LCM) treatment on oxidative stress and inflammatory damage in a model of pilocarpine-induced SE. Methods: Male Wistar rats were randomly divided into six groups and the two antiepileptic drugs (AEDs), TPM (40 and 80 mg/kg, i.p.) and LCM (10 and 30 mg/kg, i.p.), were injected three times repeatedly after pilocarpine administration. Rats were sacrificed 24 h post-SE and several parameters of oxidative stress and inflammatory response have been explored in the hippocampus. Results: The two drugs TPM and LCM, in both doses used, succeeded in attenuating the number of motor seizures compared to the SE-veh group 30 min after administration. Pilocarpine-induced SE decreased the superoxide dismutase (SOD) activity and reduced glutathione (GSH) levels while increasing the catalase (CAT) activity, malondialdehyde (MDA), and IL-1β levels compared to the control group. Groups with SE did not affect the TNF-α levels. The treatment with a higher dose of 30 mg/kg LCM restored to control level the SOD activity in the SE group. The two AEDs, in both doses applied, also normalized the CAT activity and MDA levels to control values. In conclusion, we suggest that the antioxidant effect of TPM and LCM might contribute to their anticonvulsant effect against pilocarpine-induced SE, whereas their weak anti-inflammatory effect in the hippocampus is a consequence of reduced SE severity.

Pre- and Post-Endurance Training Mitigates the Rat Pilocarpine-Induced Status Epilepticus and Epileptogenesis-Associated Deleterious Consequences

“…As previously described, SE was induced by an intraperitoneal injection of Pilo (320 mg/kg), 30 minutes after administration of scopolamine methyl nitrate 1 mg/kg i.p [ 61 , 62 ]. Seizure severity was evaluated based on the Racine scale [ 63 ].…”

“…The object recognition protocol (ORT) consisted of a sample session and a test session. The ORT was carried out as previously described [ 62 , 65 ]. The time (s) needed to explore the familiar (A) and novel (B) objects was recorded during the test session.…”

“…A sucrose preference test was performed in order to assess depressive-like behavior, as previously described [ 62 , 65 ]. The test was carried out on 3 consecutive days, and the consumed sucrose solution and water (in mL) were measured on the 3rd (test) day.…”

“…As previously reported, the elevated plus maze test was performed in order to evaluate the anxiety-like behavior [ 62 , 65 ]. In brief, the following behavioral parameters were determined: duration and number of entries in open arms and closed arms.…”

Histopathological and Biochemical Assessment of Neuroprotective Effects of Sodium Valproate and Lutein on the Pilocarpine Albino Rat Model of Epilepsy

“…Comparable discoveries have been made in corresponding anatomical areas in Wistar mice and male Sprague-Dawley rats [ 43 – 45 ]. Interestingly, this astrocyte increase was associated with the diminished population of normal nerve cells in these territories in rodents receiving six PTZ injections [ 46 ]. Heat shock protein- (HSP-) 27 is liberated from astrocytes; a rise in its concentration is associated with an increasing abundance of astrocyte cells.…”