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

Clinically, temporal lobe epilepsy (TLE) is the most prevalent type of partial epilepsy and often accompanied by various comorbidities. The present study aimed to evaluate the effects of chronic treatment with the antiepileptic drug (AED) lacosamide (LCM) on spontaneous motor seizures (SMS), behavioral comorbidities, oxidative stress, neuroinflammation, and neuronal damage in a model of TLE. Vehicle/LCM treatment (30 mg/kg, p.o.) was administered 3 h after the pilocarpine-induced status epilepticus (SE) and continued for up to 12 weeks in Wistar rats. Our study showed that LCM attenuated the number of SMS and corrected comorbid to epilepsy impaired motor activity, anxiety, memory, and alleviated depressive-like responses measured in the elevated plus maze, object recognition test, radial arm maze test, and sucrose preference test, respectively. This AED suppressed oxidative stress through increased superoxide dismutase activity and glutathione levels, and alleviated catalase activity and lipid peroxidation in the hippocampus. Lacosamide treatment after SE mitigated the increased levels of IL-1β and TNF-α in the hippocampus and exerted strong neuroprotection both in the dorsal and ventral hippocampus, basolateral amygdala, and partially in the piriform cortex. Our results suggest that the antioxidant, anti-inflammatory, and neuroprotective activity of LCM is an important prerequisite for its anticonvulsant and beneficial effects on SE-induced behavioral comorbidities

Protective effect of lacosamide and topiramate treatment against Pentylenetetrazole-induced kindling and associated cognitive dysfunction in rats

Cognitive impairment is considered the most common comorbidity in epilepsy. The aim of the present study was to explore the effects of long-term treatment with lacosamide and topiramate on epileptogenesis and related cognitive dysfunction in an experimental model of pentylenetetrazole (PTZ)-induced kindling. The latter was induced by the repeated administration of subconvulsive dose of PTZ (40 mg/kg, s.c.) on every alternate day for 8–9 weeks. Both drugs were applied daily in a dose of 10 mg/kg p.o. 30 min before PTZ injection. To assess behavioral comorbidities all rats underwent one active and one passive avoidance tests. The results show that lacosamide significantly suppressed the progression of kindling, while the effect of topiramate was not so pronounced on seizure development. Long-term treatment with both antiepileptic drugs managed to ameliorate the kindling-associated impairment of learning and memory. Lacosamide and topiramate improved active and passive learning abilities and facilitated the formation of short- and long-term memory traces. Both drugs failed to prevent the hyperactivity associated with epilepsy

Oral Microbial Flora in Bulgarian Adolescents with Moderate Plaque-induced Gingivitis

Introduction: In children and adolescents, the most common periodontal disease is the plaque-induced gingivitis.Aim: The aim of this study was to reveal the bacterial species associated with supragingival plaque of Bulgarian adolescents diagnosed with plaque-induced gingivitis.Materials and methods: Supragingival plaque samples from 70 healthy subjects with moderate plaque-induced gingivitis (37 females and 33 males), aged 12-18 years, were obtained and examined microbiologically.Results: A total of 224 microorganisms were isolated. Gram-negative bacteria were predominant compared to Gram-positive [132 (59%) vs. 92 (41%), p<0.001]. Aerobic microorganisms were detected more often than anaerobic (151; 67.5% vs. 73; 32.5%, p<0.001). The Streptococcus mutans group and Neisseria spp. were isolated from all adolescents. The frequency of isolation of C. albicans was relatively lower – 11 (15.7%). The anaerobes showed much greater microbial diversity (12 pathogen groups were isolated). Gram-negative rods were isolated from 57 of the adolescents (isolation frequency 81.4%). F. varium, P. melaninogenica, P. intermedia and P. assacharolyticus were detected respectively in 12 (16%), 9 (12%), 8 (11%) and 7 (10%) samples. The less frequently isolated anaerobes were Gram-positive cocci, Gram-negative cocci, Bacteroides uniformis and Bifidobacterium spp. together.Conclusion: The most frequently isolated microbiota in our study is part of the normal oral bacterial flora. The presence of anaerobes such as Prevotella, Fusobacterium, Bacteroides and Porphyromonas reflects the gradual change of the flora to more complex one. The results of quantitative and qualitative evaluation of the plaque of adolescents with moderate plaque-induced gingivitis may contribute to the selection of the prevention and treatment of this disease

The Effect of Chronic Treatment with Lacosamide and Topiramate on Cognitive Functions and Impaired Emotional Responses in a Pilocarpine-induced Post-status Epilepticus Rat Model

Introduction: Epilepsy and antiepileptic drugs can affect negatively the cognitive abilities of patients.Aim: The present study aimed to evaluate the effect of topiramate (TPM) and lacosamide (LCM) on the emotional and cognitive re-sponses in naive animals and in animals with pilocarpine-induced status epilepticus. Materials and methods: Male Wistar rats were randomly divided into 6 groups and status epilepticus was evoked in half of them by a single i.p. administration of pilocarpine (Pilo) (320 mg/kg): Pilo-veh, Pilo-TPM (80 mg/kg) and Pilo-LCM (30 mg/kg). Matched naive rats were treated with the same doses as follows: C-veh, C-TPM, and C-LCM. In a step-down passive avoidance test, the learning session was held for one day, the early retention test was conducted on day 2, and the long-term memory test - on day 7. Motor activity and anxiety were evaluated in an open field test. Results: The Pilo-TPM and Pilo-LCM groups increased the time spent on the platform compared to Pilo-veh animals while the C-LCM animals decreased the time compared to C-veh animals during short- and long-term memory retention tests. TPM and LCM exerted an anxiolytic effect in naive rats. The two antiepileptic drugs were unable to alleviate the hyperactivity, but they alleviated the impulsivity associated with decreased anxiety level in epileptic rats.Conclusions: Our findings suggest that LCM and TPM have a beneficial effect on cognition both in naive and epileptic rats. While the two antiepileptic drugs can produce an anxiolytic effect in naive rats, they alleviate the impulsivity after pilocarpine treatment

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

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

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

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