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

Abstract

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.

• Authors: Michaela Shishmanova-Doseva, Dimitrinka Atanasova, Yordanka Uzunova, Lyubka Yoanidu, Lyudmil Peychev, Pencho Marinov, Jana Tchekalarova
• Journal: International journal of molecular sciences (Int J Mol Sci) Vol. 22 Issue 9 (Apr 28 2021) ISSN: 1422-0067 [Electronic] Switzerland
• PMID: 33925082 (Publication Type: Journal Article)

Chemical References

• Anti-Inflammatory Agents, Non-Steroidal
• Anticonvulsants
• Antioxidants
• Neuroprotective Agents
• Pilocarpine
• Lacosamide

Topics

• Animals
• Anti-Inflammatory Agents, Non-Steroidal (therapeutic use)
• Anticonvulsants (therapeutic use)
• Antioxidants (therapeutic use)
• Behavior, Animal (drug effects)
• Disease Models, Animal
• Epilepsy, Temporal Lobe (drug therapy, pathology, physiopathology)
• Hippocampus (drug effects, pathology)
• Lacosamide (therapeutic use)
• Male
• Neurons (drug effects, pathology)
• Neuroprotective Agents (therapeutic use)
• Oxidative Stress (drug effects)
• Pilocarpine (toxicity)
• Rats
• Rats, Wistar
• Status Epilepticus (chemically induced, drug therapy)