Inverted-U response of lacosamide on pilocarpine-induced status epilepticus and oxidative stress in C57BL/6 mice is independent of hippocampal collapsin response mediator protein-2

Nirwan, Nikita; Siraj, Fouzia; Vohora, Divya

doi:10.1016/j.eplepsyres.2018.06.009

Cited by 20 publications

(20 citation statements)

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“…The present results agree with those of our previous experiment in which the repeated LCM administration suppressed the KA-induced SE and epileptogenesis in rats [24]. These data coincide with Nirwan et al [25] who also proved that LCM can mitigate the Pilo-induced SE in mice at doses of 20 and 40 mg/kg, respectively. The anticonvulsant and neuroprotective potency of LCM is due to its ability to suppress the interictal spike rates, the high-frequency oscillations in the hippocampus, as well as the mossy fiber sprouting and the loss of hippocampal neurons [26,27].…”

Section: Discussionsupporting

confidence: 93%

“…Here, we report that LCM at its higher dose of 30 mg/kg managed to increase the enzyme activity, which in turn, could protect proteins from oxidation and reduce undesired structural and functional changes in some key enzymes. Our present findings in the Piloinduced SE rat model and those of Nirwan et al [25] in the same model in mice suggest that the antioxidant effect of LCM is an important mechanism underlying the ability of this AED to mitigate SE and its devastating consequences. Nirwan et al [25] reported that LCM, administered at the same doses used as in our experimental protocol, exerted a biphasic activity with a potent anticonvulsant, antioxidant, and neuroprotective effect against Pilo-induced SE in mice.…”

Section: Discussionsupporting

confidence: 79%

“…Our present findings in the Piloinduced SE rat model and those of Nirwan et al [25] in the same model in mice suggest that the antioxidant effect of LCM is an important mechanism underlying the ability of this AED to mitigate SE and its devastating consequences. Nirwan et al [25] reported that LCM, administered at the same doses used as in our experimental protocol, exerted a biphasic activity with a potent anticonvulsant, antioxidant, and neuroprotective effect against Pilo-induced SE in mice. However, these authors revealed that LCM was inactive at a high dose of 80 mg/kg against both recurrent seizures and concomitant oxidative stress as well.…”

Section: Discussionsupporting

confidence: 79%

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

Shishmanova-Doseva

Peychev

Yoanidu

et al. 2021

IJMS

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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.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 79%

Section: Discussionsupporting

confidence: 79%

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

Shishmanova-Doseva

Peychev

Yoanidu

et al. 2021

IJMS

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“…an increased seizure threshold and pro‐convulsive effect when high doses of LCM were used. In addition, Nirwan et al [16] have demonstrated that LCM at 20 and 40 mg/kg protected against status epilepticus, whereas at 80 mg/kg promoted worsening of convulsive behavior and neurodegeneration in the regions of the hippocampus. Drugs such as oxcarbazepine used to treat epilepsy have been shown to develop toxicity in higher concentrations increasing ROS [48].…”

Section: Discussionmentioning

confidence: 99%

“…All drugs were dissolved in saline (NaCl 0.9%) solution. The doses of LCM and DZP were chosen based on previous studies [14–17]. The PTZ dose used was 50 mg/kg s.c., obtained through a pilot test.…”

Section: Methodsmentioning

confidence: 99%

Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ‐kindling model in mice

Lazzarotto

Pflüger

Regner

et al. 2020

Fundamemntal Clinical Pharma

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This study evaluated the effect of lacosamide (LCM) on biochemical and mitochondrial parameters after PTZ kindling in mice. Male mice were treated on alternative days for a period of 11 days with LCM (20, 30, or 40 mg/kg), saline, or diazepam (2 mg/kg), before PTZ administration (50 mg/kg). The hippocampi were collected to evaluate free radicals, the activities of superoxide dismutase (SOD), catalase (CAT), and the mitochondrial complexes I‐III, II, and II‐III, as well as Bcl‐2 and cyclo‐oxygenase‐2 (COX‐2) expressions. Hippocampi, blood, and bone marrow were collected for genotoxic and mutagenic evaluations. LCM 40 mg/kg increased latency and decreased percentage of seizures, only on the 3rd day of observation. The dose of 30 mg/kg only showed positive effects on the percentage of seizures on the 2nd day of observation. LCM decreased free radicals and SOD activity and the dose of 40 mg/kg were able to increase CAT activity. LCM 30 and 40 mg/kg improved the enzymatic mitochondrial activity of the complex I‐III and LCM 30 mg/kg improved the activity of the complex II. In the comet assay, the damage induced by PTZ administration was reduced by LCM 20 and 30 mg/kg. The dose of 20 mg/kg increased COX‐2 expression while the highest dose used, 40 mg/kg, was able to reduce this expression when compared to the group treated with LCM 20 mg/kg. Although LCM did not produce the antiepileptogenic effect in vivo, it showed the neuroprotective effect against oxidative stress, bioenergetic dysfunction, and DNA damage induced by the repeated PTZ administration.

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The Impact of Prophylactic Lacosamide on LPS-Induced Neuroinflammation in Aged Rats

et al. 2019

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Inverted-U response of lacosamide on pilocarpine-induced status epilepticus and oxidative stress in C57BL/6 mice is independent of hippocampal collapsin response mediator protein-2

Cited by 20 publications

References 50 publications

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

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

Lacosamide improves biochemical, genotoxic, and mitochondrial parameters after PTZ‐kindling model in mice

The Impact of Prophylactic Lacosamide on LPS-Induced Neuroinflammation in Aged Rats

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