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.
Highlights
Status epilepticus (SE) is a clinical condition characterized by prolonged or short-term but repeated seizures activity [1]
The two antiepileptic drugs (AEDs) alleviated the seizure frequency compared to the SE-veh group at the 150th min, i.e., thirty minutes after the first injection, as well as at the 270th min after SE, at doses of 40 and 80 mg/kg for TPM (p < 0.001), and at doses of 10 and 30 mg/kg for LCM (p < 0.001), respectively
We found that the two AEDs, mainly used as the 2nd and 3rd line drugs in clinical practice, and given repeatedly, after the onset of SE, at doses of 40 and 80 mg/kg, for TPM, and at doses of 10 and 30 mg/kg, for LCM, respectively, suppressed behavioral motor seizures and accompanying oxidative stress, and partially mitigated SE-induced neuroinflammation in the hippocampus
Summary
Status epilepticus (SE) is a clinical condition characterized by prolonged or short-term but repeated seizures activity [1]. It results in epileptogenesis with devastating plastic changes in vulnerable brain structures, including decreased seizure threshold and neuronal injury [2,3]. Reactive oxygen species (ROS), such as the superoxide radical, hydroxyl radical, singlet oxygen, as well as subsequently produced reactive nitrogen species (peroxynitrite anion), have been scavenged by several antioxidant systems These could be either enzymatic systems— catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR)—or nonenzymatic antioxidants—reduced glutathione (GSH) and vitamins C and E [7]. 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
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