Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy
Efficient treatment of temporal lobe epilepsy (TLE) remains challenging due to limited understanding of cellular and network changes and the interference of novel antiepileptic drugs (AEDs) with tissue reorganisation. This study compared the effects of brivaracetam and levetiracetam on histological...
Saved in:
| Main Authors: | , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2025-03-01
|
| Series: | Frontiers in Pharmacology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2025.1553545/full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849773222300483584 |
|---|---|
| author | Krisztina Kelemen Krisztina Kelemen Krisztina Kelemen Máté Sárosi Ágnes Csüdör Károly Orbán-Kis Hanga Kelemen Hanga Kelemen László Bába Zsolt Gáll Eszter Horváth István Katona István Katona Tibor Szilágyi |
| author_facet | Krisztina Kelemen Krisztina Kelemen Krisztina Kelemen Máté Sárosi Ágnes Csüdör Károly Orbán-Kis Hanga Kelemen Hanga Kelemen László Bába Zsolt Gáll Eszter Horváth István Katona István Katona Tibor Szilágyi |
| author_sort | Krisztina Kelemen |
| collection | DOAJ |
| description | Efficient treatment of temporal lobe epilepsy (TLE) remains challenging due to limited understanding of cellular and network changes and the interference of novel antiepileptic drugs (AEDs) with tissue reorganisation. This study compared the effects of brivaracetam and levetiracetam on histological alterations in key brain regions of the epileptic circuitry, namely, the hippocampus, amygdala, piriform cortex (PC), endopiriform nucleus (EPN) and paraventricular thalamic nucleus (PVT), using the kainic acid (KA) rat model of TLE. Male Wistar rats were assigned to sham-operated (SHAM), epileptic (EPI), brivaracetam- (BRV-EPI) and levetiracetam-treated (LEV-EPI) epileptic groups. Epileptic groups received KA in the right lateral ventricle, which induced status epilepticus followed by a 3-week recovery and latent period. Rats then underwent 3 weeks of oral brivaracetam, levetiracetam or placebo treatment with continuous video monitoring for seizure analysis. Subsequently, triple fluorescent immunolabeling assessed microglial, astrocytic, and neuronal changes. The results showed a drastic increase in microglia density in the EPI and BRV-EPI groups compared to control and LEV-EPI. The BRV-EPI group displayed a significantly higher microglia density than SHAM and EPI groups in the right CA1, CA3 and left CA1 regions, bilateral amygdalae, EPN, PVT and left PC. Astrocyte density was significantly elevated in hippocampal regions of the BRV-EPI group, while neuronal density decreased. Furthermore, brivaracetam did not reduce seizure activity in this disease phase. Significance: Brivaracetam treatment increased microglial activation under epileptic conditions in vivo in all examined brain-regions participating in the epileptic circuitry, in contrast to the effects of levetiracetam, highlighting differences in AED-induced histological alterations. |
| format | Article |
| id | doaj-art-71028a67c15440efab5a75720d64bfc9 |
| institution | DOAJ |
| issn | 1663-9812 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj-art-71028a67c15440efab5a75720d64bfc92025-08-20T03:02:07ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122025-03-011610.3389/fphar.2025.15535451553545Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsyKrisztina Kelemen0Krisztina Kelemen1Krisztina Kelemen2Máté Sárosi3Ágnes Csüdör4Károly Orbán-Kis5Hanga Kelemen6Hanga Kelemen7László Bába8Zsolt Gáll9Eszter Horváth10István Katona11István Katona12Tibor Szilágyi13Department of Physiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, RomaniaDoctoral School, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, RomaniaMolecular Neurobiology Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryFaculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, RomaniaFaculty of Medicine, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, RomaniaDepartment of Physiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, RomaniaTranslational Behavioural Neuroscience Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryJános Szentágothai Neurosciences Division, Doctoral College, Semmelweis University, Budapest, HungaryDepartment of Pharmacology and Clinical Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Târgu Mures, RomaniaDepartment of Pharmacology and Clinical Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Targu Mures, Târgu Mures, RomaniaMolecular Neurobiology Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryMolecular Neurobiology Research Group, HUN-REN Institute of Experimental Medicine, Budapest, HungaryDepartment of Psychological and Brain Sciences, Indiana University Bloomington, Bloomington, IN, United StatesDepartment of Physiology, George Emil Palade University of Medicine, Pharmacy, Science, and Technology of Targu Mures, Târgu Mureș, RomaniaEfficient treatment of temporal lobe epilepsy (TLE) remains challenging due to limited understanding of cellular and network changes and the interference of novel antiepileptic drugs (AEDs) with tissue reorganisation. This study compared the effects of brivaracetam and levetiracetam on histological alterations in key brain regions of the epileptic circuitry, namely, the hippocampus, amygdala, piriform cortex (PC), endopiriform nucleus (EPN) and paraventricular thalamic nucleus (PVT), using the kainic acid (KA) rat model of TLE. Male Wistar rats were assigned to sham-operated (SHAM), epileptic (EPI), brivaracetam- (BRV-EPI) and levetiracetam-treated (LEV-EPI) epileptic groups. Epileptic groups received KA in the right lateral ventricle, which induced status epilepticus followed by a 3-week recovery and latent period. Rats then underwent 3 weeks of oral brivaracetam, levetiracetam or placebo treatment with continuous video monitoring for seizure analysis. Subsequently, triple fluorescent immunolabeling assessed microglial, astrocytic, and neuronal changes. The results showed a drastic increase in microglia density in the EPI and BRV-EPI groups compared to control and LEV-EPI. The BRV-EPI group displayed a significantly higher microglia density than SHAM and EPI groups in the right CA1, CA3 and left CA1 regions, bilateral amygdalae, EPN, PVT and left PC. Astrocyte density was significantly elevated in hippocampal regions of the BRV-EPI group, while neuronal density decreased. Furthermore, brivaracetam did not reduce seizure activity in this disease phase. Significance: Brivaracetam treatment increased microglial activation under epileptic conditions in vivo in all examined brain-regions participating in the epileptic circuitry, in contrast to the effects of levetiracetam, highlighting differences in AED-induced histological alterations.https://www.frontiersin.org/articles/10.3389/fphar.2025.1553545/fulltemporal lobe epilepsy (TLE)antiepileptic drugsmicroglia-activationbrain-regionsepileptic circuitry |
| spellingShingle | Krisztina Kelemen Krisztina Kelemen Krisztina Kelemen Máté Sárosi Ágnes Csüdör Károly Orbán-Kis Hanga Kelemen Hanga Kelemen László Bába Zsolt Gáll Eszter Horváth István Katona István Katona Tibor Szilágyi Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy Frontiers in Pharmacology temporal lobe epilepsy (TLE) antiepileptic drugs microglia-activation brain-regions epileptic circuitry |
| title | Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy |
| title_full | Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy |
| title_fullStr | Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy |
| title_full_unstemmed | Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy |
| title_short | Marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial, astrocytic, and neuronal density in the rat model of kainic acid-induced temporal lobe epilepsy |
| title_sort | marked differences in the effects of levetiracetam and its analogue brivaracetam on microglial astrocytic and neuronal density in the rat model of kainic acid induced temporal lobe epilepsy |
| topic | temporal lobe epilepsy (TLE) antiepileptic drugs microglia-activation brain-regions epileptic circuitry |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2025.1553545/full |
| work_keys_str_mv | AT krisztinakelemen markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT krisztinakelemen markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT krisztinakelemen markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT matesarosi markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT agnescsudor markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT karolyorbankis markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT hangakelemen markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT hangakelemen markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT laszlobaba markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT zsoltgall markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT eszterhorvath markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT istvankatona markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT istvankatona markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy AT tiborszilagyi markeddifferencesintheeffectsoflevetiracetamanditsanaloguebrivaracetamonmicroglialastrocyticandneuronaldensityintheratmodelofkainicacidinducedtemporallobeepilepsy |