Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

Shishmanova-Doseva, Michaela; Atanasova, Dimitrinka; Uzunova, Yordanka; Yoanidu, Lyubka; Peychev, Lyudmil; Marinov, Pencho; Tchekalarova, Jana

doi:10.3390/ijms22094667

Cited by 12 publications

(5 citation statements)

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“…These results are similar to those of Mishra et al (2021a) and suggest anti-amnesic-and anxiolytic-like properties. These findings confirm the antiepileptogenic potential of the plant extract since working memory impairment, anxiety disorders, and epileptogenesis share similar bidirectional and cause-toeffect links (Shishmanova-Doseva et al, 2021;Suleymanova, 2021).…”

Section: Discussionsupporting

confidence: 76%

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

et al. 2022

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Parkia biglobosa (Jacq.) R. Br. (Fabaceae) is a widely distributed tree, used in traditional medicine to treat amebiasis, hookworm infection, ascariasis, asthma, sterility, dental pain, headaches, cardiac disorders, and epilepsy. To date, no study on the effect of an aqueous extract of P. biglobosa on epileptogenesis and associated neuropsychiatric disorders has been undertaken. Therefore, this study aimed to investigate antiepileptogenic-, antiamnesic-, and anxiolytic-like effects of an aqueous extract of P. biglobosa using pentylenetetrazole (PTZ)-induced kindling in mice. Animals were divided into six groups of eight mice each. Thus, a PTZ group received distilled water (10 ml/kg, per os), a positive control group received sodium valproate (300 mg/kg, p.o.), and three test groups received the aqueous extract of P. biglobosa (80, 160, and 320 mg/kg, p.o.).In addition, a control group of eight mice receiving distilled water (10 ml/kg, p.o.) was formed. The treatments were administered to mice, 60 min before administration of PTZ (20 mg/kg, i.p.). These co-administrations were performed once daily, for 22 days. The number and duration of seizures (stages 1, 2, 3, and 4 of seizures) exhibited by each mouse were assessed for 30 min during the treatment period. Twenty-four hours following the last administration of the treatments and PTZ, novel object recognition and T-maze tests were performed to assess working memory impairment in mice, while the open field test was performed to assess anxiety-like behavior. After these tests, the animals were sacrificed, and the hippocampi were collected for biochemical and histological analysis. During the period of PTZ-kindling, the extract at all doses completely (p < 0.001) protected all mice against stages 3 and 4 of seizures when compared to sodium valproate, a standard antiepileptic drug. The extract also significantly (p < 0.001) attenuated working memory impairment and anxiety-like behavior. In post-mortem brain analyses, the extract significantly (p < 0.001) increased γ-aminobutyric acid (GABA) level and reduced oxidative stress and inflammation. Histological analysis showed that the aqueous extract attenuated neuronal degeneration/necrosis in the hippocampus. These results suggest that the extract is endowed with antiepileptogenic-, anti-amnesic-, and anxiolytic-like effects. These effects seem to be mediated in part by GABAergic, antioxidant, and anti-inflammatory mechanisms. These results suggest the merit of further studies to isolate the bioactive molecules responsible for these potentially therapeutically relevant effects of the extract.

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Section: Discussionsupporting

confidence: 76%

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

et al. 2022

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“…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 ].…”

Section: Materials and Methodsvmentioning

confidence: 99%

“…The anxiety index (AI) was calculated as follows: AI = 1 − [(open arms time/total time) + (number of entries in open arms/total number of entries)/2]. The alleys of the maze were cleaned with ethanol solution (60% volume) after the removal of each rat [ 63 , 65 ].…”

Section: Materials and Methodsvmentioning

confidence: 99%

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

Shishmanova-Doseva

Georgieva²,

Uzunova³

et al. 2022

IJMS

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Epilepsy is a brain disorder characterized by recurrent epileptic seizures and neurobiological, physiological, mood, and cognitive consequences. In the last decade, the beneficial effects of regular physical exercise have been investigated in patients with neurodegenerative diseases such as epilepsy. However, data on its beneficial effects and underlying mechanisms are still insufficient. The objective of the current study was to investigate the effects of endurance training, applied before and after pilocarpine (Pilo) administration, on status epilepticus (SE) severity, and its relation to epileptogenesis deleterious consequences during the chronic epileptic phase. Long-term aerobic training, applied four weeks before SE and eight weeks after SE, elevated the threshold to induce SE and reduced spontaneous motor seizures. The protective effect of this alternative approach on seizure susceptibility resulted in improved memory responses, and alleviated comorbid depression in epileptic rats. The exercised epileptic rats had improved markers of oxidative stress by decreasing lipid peroxidation and increasing the levels of glutathione and activity of superoxide dismutase in the rat hippocampus. Aerobic training managed to ameliorate the neuroinflammation by decreasing the levels of TNF-α and IL-1β in the hippocampus. Our results suggest that regular physical training predisposes the subjects to crucial plastic changes, leading to increased resistance to SE and the development of epileptogenesis.

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“…These data show that the inhibition of the TLR4/NF-κB inflammatory pathway can improve the emotional and behavioral disorders of epileptic rats. Studies have shown that a large number of hippocampal neurons die after epileptic seizure ( 25 , 50 – 52 ), which may be related to microglias promoting epileptic-induced neurogenesis ( 53 , 54 ). In the TUNEL experiment, neuronal apoptosis was greater in rats in the EP group, and the expression in rats in the two treatment groups, the EP+BAY group and EP+TAK group, was better than that of rats in the EP group.…”

Section: Discussionmentioning

confidence: 99%

The Role of the Negative Regulation of Microglia-Mediated Neuroinflammation in Improving Emotional Behavior After Epileptic Seizures

Wang

Liu

et al. 2022

Front. Neurol.

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ObjectiveStudies have long shown that uncontrolled inflammatory responses in the brain play a key role in epilepsy pathogenesis. Microglias play an important role in epileptic-induced neuroinflammation, but their role after epileptic seizures is still poorly understood. Alleviating epilepsy and its comorbidities has become a key area of interest for pediatricians.MethodsA pilocarpine-induced rat model of epilepsy was established. The rats were randomly divided into four groups: a control group, epilepsy group, TLR4 inhibitor group (epilepsy+TAK-242), and NF-κB antagonist group (epilepsy+BAY11–7082).Results1. The results of TUNEL staining showed that the expression in rats in the epilepsy group was the most obvious and was significantly different from that in rats in the control, EP+BAY and EP+TAK groups. 2. The expression of TLR4 and NF-κB was highest in rats in the epilepsy group and was significantly different from that in rats in the control, EP+BAY and EP+TAK groups. 3. The fluorescence intensity and number of IBA-1-positive cells in rats in the epilepsy group were highest and significantly different from those in rats in the control, EP+BAY and EP+TAK groups. Western blot analysis of IBA-1 showed that the expression in rats in the epilepsy group was the highest and was statistically significant. 4. CD68 was the highest in rats in the epilepsy group and was statistically significant. 5. In the open-field experiment, the central region residence time of rats in the EP group was delayed, the central region movement distance traveled was prolonged, the total distance traveled was prolonged, and the average speed was increased. Compared with rats in the EP group, rats in the EP+BAY and EP+ TAK groups exhibited improvements to different degrees.ConclusionAt the tissue level, downregulation of the TLR4/NF-κB inflammatory pathway in epilepsy could inhibit microglial activation and the expression of the inflammatory factor CD68, could inhibit hyperphagocytosis, and inhibit the occurrence and exacerbation of epilepsy, thus improving cognitive and emotional disorders after epileptic seizures.

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Effects of Lacosamide Treatment on Epileptogenesis, Neuronal Damage and Behavioral Comorbidities in a Rat Model of Temporal Lobe Epilepsy

Cited by 12 publications

References 76 publications

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

Aqueous extract of Parkia biglobosa (Jacq.) R. Br. (Fabaceae) exerts antiepileptogenic, anti-amnesic, and anxiolytic-like effects in mice via mechanisms involving antioxidant and anti-inflammatory pathways

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

The Role of the Negative Regulation of Microglia-Mediated Neuroinflammation in Improving Emotional Behavior After Epileptic Seizures

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