Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats
Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no...
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2023-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/20/15400 |
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| author | Olga E. Zubareva Denis S. Sinyak Alisa D. Kalita Alexandra V. Griflyuk Georgy P. Diespirov Tatiana Y. Postnikova Aleksey V. Zaitsev |
| author_facet | Olga E. Zubareva Denis S. Sinyak Alisa D. Kalita Alexandra V. Griflyuk Georgy P. Diespirov Tatiana Y. Postnikova Aleksey V. Zaitsev |
| author_sort | Olga E. Zubareva |
| collection | DOAJ |
| description | Temporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that there was no significant difference in the number and duration of seizures between treated and untreated animals. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective in preventing neuron loss in the hippocampal CA3 field compared to combination treatment. The treatment alleviated the impairments in activity level, exploratory behavior, and anxiety but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, either alone or in combination, may be clinically useful in preventing the development of histopathological and behavioral abnormalities associated with epilepsy. |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T21:12:12Z |
| publishDate | 2023-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d4ea372154594d36a3e5d743b8075cf82023-11-19T16:46:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-10-0124201540010.3390/ijms242015400Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in RatsOlga E. Zubareva0Denis S. Sinyak1Alisa D. Kalita2Alexandra V. Griflyuk3Georgy P. Diespirov4Tatiana Y. Postnikova5Aleksey V. Zaitsev6Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaSechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of Sciences, 194223 Saint Petersburg, RussiaTemporal lobe epilepsy is a common, chronic disorder with spontaneous seizures that is often refractory to drug therapy. A potential cause of temporal lobe epilepsy is primary brain injury, making prevention of epileptogenesis after the initial event an optimal method of treatment. Despite this, no preventive therapy for epilepsy is currently available. The purpose of this study was to evaluate the effects of anakinra, lamotrigine, and their combination on epileptogenesis using the rat lithium-pilocarpine model of temporal lobe epilepsy. The study showed that there was no significant difference in the number and duration of seizures between treated and untreated animals. However, the severity of seizures was significantly reduced after treatment. Anakinra and lamotrigine, alone or in combination, significantly reduced neuronal loss in the CA1 hippocampus compared to the control group. However, the drugs administered alone were found to be more effective in preventing neuron loss in the hippocampal CA3 field compared to combination treatment. The treatment alleviated the impairments in activity level, exploratory behavior, and anxiety but had a relatively weak effect on TLE-induced impairments in social behavior and memory. The efficacy of the combination treatment did not differ from that of anakinra and lamotrigine monotherapy. These findings suggest that anakinra and lamotrigine, either alone or in combination, may be clinically useful in preventing the development of histopathological and behavioral abnormalities associated with epilepsy.https://www.mdpi.com/1422-0067/24/20/15400temporal lobe epilepsyanakinralithium–pilocarpine modelbehaviorepileptogenesishippocampus |
| spellingShingle | Olga E. Zubareva Denis S. Sinyak Alisa D. Kalita Alexandra V. Griflyuk Georgy P. Diespirov Tatiana Y. Postnikova Aleksey V. Zaitsev Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats International Journal of Molecular Sciences temporal lobe epilepsy anakinra lithium–pilocarpine model behavior epileptogenesis hippocampus |
| title | Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats |
| title_full | Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats |
| title_fullStr | Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats |
| title_full_unstemmed | Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats |
| title_short | Antiepileptogenic Effects of Anakinra, Lamotrigine and Their Combination in a Lithium–Pilocarpine Model of Temporal Lobe Epilepsy in Rats |
| title_sort | antiepileptogenic effects of anakinra lamotrigine and their combination in a lithium pilocarpine model of temporal lobe epilepsy in rats |
| topic | temporal lobe epilepsy anakinra lithium–pilocarpine model behavior epileptogenesis hippocampus |
| url | https://www.mdpi.com/1422-0067/24/20/15400 |
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