Translational potential of the ghrelin receptor agonist macimorelin for seizure suppression in pharmacoresistant epilepsy
| Autor: | Ilse Julia Smolders, Dimitri De Bundel, Eckhard Guenther, Ron Kooijman, Yana Van Den Herrewegen, An Buckinx, Anouk Pierre, Gaetan Van Laethem, Matthias Gerlach |
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| Přispěvatelé: | Mathematics, Faculty of Medicine and Pharmacy, Pharmaceutical and Pharmacological Sciences, Experimental Pharmacology, Basic (bio-) Medical Sciences |
| Rok vydání: | 2021 |
| Předmět: |
Agonist
Kainic acid Indoles medicine.drug_class medicine.medical_treatment Status epilepticus Pharmacology Hippocampus Epileptogenesis Neuroprotection Mice chemistry.chemical_compound Epilepsy Status Epilepticus Seizures medicine Animals Humans Receptors Ghrelin business.industry Tryptophan Electroencephalography medicine.disease Mice Inbred C57BL Disease Models Animal Anticonvulsant Epilepsy Temporal Lobe Neurology chemistry Ghrelin Neurology (clinical) medicine.symptom business |
| Zdroj: | European Journal of Neurology. 28:3100-3112 |
| ISSN: | 1468-1331 1351-5101 |
| DOI: | 10.1111/ene.14992 |
| Popis: | Background Current drugs for epilepsy affect seizures, but no antiepileptogenic or disease-modifying drugs are available that prevent or slow down epileptogenesis, which is characterized by neuronal cell loss, inflammation and aberrant network formation. Ghrelin and ghrelin receptor (ghrelin-R) agonists were previously found to exert anticonvulsant, neuroprotective and anti-inflammatory effects in seizure models and immediately after status epilepticus (SE). Therefore, the aim of this study was to assess whether the ghrelin-R agonist macimorelin is antiepileptogenic in the pharmacoresistant intrahippocampal kainic acid (IHKA) mouse model. Methods SE was induced in C57BL/6 mice by unilateral IHKA injection. Starting 24 h after SE, mice were treated intraperitoneally with macimorelin (5 mg/kg) or saline twice daily for 2 weeks, followed by a 2-week wash-out. Mice were continuously electroencephalogram-monitored, and at the end of the experiment neuroprotection and gliosis were assessed. Results Macimorelin significantly decreased the number and duration of seizures during the treatment period, but had no antiepileptogenic or disease-modifying effect in this dose regimen. While macimorelin did not significantly affect food intake or body weight over a 2-week treatment period, its acute orexigenic effect was preserved in epileptic mice but not in sham mice. Conclusions While the full ghrelin-R agonist macimorelin was not significantly antiepileptogenic nor disease-modifying, this is the first study to demonstrate its anticonvulsant effects in the IHKA model of drug-refractory temporal lobe epilepsy. These findings highlight the potential use of macimorelin as a novel treatment option for seizure suppression in pharmacoresistant epilepsy. |
| Databáze: | OpenAIRE |
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