TSPO PET Identifies Different Anti-inflammatory Minocycline Treatment Response in Two Rodent Models of Epileptogenesis
Uloženo v:
| Název: | TSPO PET Identifies Different Anti-inflammatory Minocycline Treatment Response in Two Rodent Models of Epileptogenesis |
|---|---|
| Autoři: | B Laura N Langer, Jens P. Bankstahl, Tobias L. Ross, Ina Leiter, Pablo Bascuñana, Marion Bankstahl, Bettina J. Wolf, Mirjam Brackhan |
| Zdroj: | Neurotherapeutics |
| Informace o vydavateli: | Elsevier BV, 2020. |
| Rok vydání: | 2020 |
| Témata: | Male, Epilepsy, Receptors, GABA-A/metabolism [MeSH], Neuroinflammation, Epilepsy/drug therapy [MeSH], Rats, Sprague-Dawley [MeSH], Epilepsy/diagnostic imaging [MeSH], Carrier Proteins/metabolism [MeSH], PET, Original Article, Minocycline/metabolism [MeSH], Positron-Emission Tomography/methods [MeSH], Male [MeSH], Disease Models, Animal [MeSH], Anti-Inflammatory Agents/metabolism [MeSH], Female [MeSH], Minocycline/therapeutic use [MeSH], Brain/diagnostic imaging [MeSH], Epilepsy/metabolism [MeSH], translocator protein, Brain/drug effects [MeSH], Treatment Outcome [MeSH], Rats [MeSH], minocycline, Animals [MeSH], Mice [MeSH], Brain/metabolism [MeSH], Radiopharmaceuticals/metabolism [MeSH], Anti-Inflammatory Agents/therapeutic use [MeSH], epileptogenesis, Anti-Inflammatory Agents, Brain, Minocycline, Receptors, GABA-A, Rats, 3. Good health, Rats, Sprague-Dawley, Disease Models, Animal, Mice, 03 medical and health sciences, Treatment Outcome, 0302 clinical medicine, Positron-Emission Tomography, Animals, Female, Radiopharmaceuticals, Carrier Proteins |
| Popis: | Epileptogenesis-associated brain inflammation might be a promising target to prevent or attenuate epileptogenesis. Positron emission tomography (PET) imaging targeting the translocator protein (TSPO) was applied here to quantify effects of different dosing regimens of the anti-inflammatory drug minocycline during the latent phase in two rodent models of epileptogenesis. After induction of epileptogenesis by status epilepticus (SE), rats were treated with minocycline for 7 days (25 or 50 mg/kg) and mice for 5 or 10 days (50 or 100 mg/kg). All animals were subjected to scans at 1 and 2 weeks post-SE. Radiotracer distribution was analyzed and statistical parametric mapping (SPM) was performed, as well as histological analysis of astroglial activation and neuronal cell loss. Atlas-based analysis of [18F]GE180 PET in rats revealed a dose-dependent regional decrease of TSPO expression at 2 weeks post-SE. Results of SPM analysis depicted a treatment effect already at 1 week post-SE in rats treated with the higher minocycline dose. In mice, TSPO PET imaging did not reveal any treatment effects whereas histology identified only a treatment-related reduction in dispersion of dentate gyrus neurons. TSPO PET served as an auspicious tool for temporal monitoring and quantification of anti-inflammatory effects during epileptogenesis. Importantly, the findings underline the need to applying more than one animal model to avoid missing treatment effects. For future studies, the setup is ready to be applied in combination with seizure monitoring to investigate the relationship between individual early treatment response and disease outcome. |
| Druh dokumentu: | Article Other literature type |
| Jazyk: | English |
| ISSN: | 1878-7479 |
| DOI: | 10.1007/s13311-020-00834-5 |
| Přístupová URL adresa: | https://link.springer.com/content/pdf/10.1007/s13311-020-00834-5.pdf https://pubmed.ncbi.nlm.nih.gov/31970667 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609777 https://pubmed.ncbi.nlm.nih.gov/31970667/ https://elib.tiho-hannover.de/receive/tiho_mods_00002117 https://link.springer.com/article/10.1007/s13311-020-00834-5 https://link.springer.com/content/pdf/10.1007/s13311-020-00834-5.pdf https://repository.publisso.de/resource/frl:6470852 |
| Rights: | CC BY |
| Přístupové číslo: | edsair.doi.dedup.....b5a7af5edb038c165421d80fb32031c1 |
| Databáze: | OpenAIRE |
Full Text 
Full Text Finder 
Nájsť tento článok vo Web of Science | Abstrakt: | Epileptogenesis-associated brain inflammation might be a promising target to prevent or attenuate epileptogenesis. Positron emission tomography (PET) imaging targeting the translocator protein (TSPO) was applied here to quantify effects of different dosing regimens of the anti-inflammatory drug minocycline during the latent phase in two rodent models of epileptogenesis. After induction of epileptogenesis by status epilepticus (SE), rats were treated with minocycline for 7 days (25 or 50 mg/kg) and mice for 5 or 10 days (50 or 100 mg/kg). All animals were subjected to scans at 1 and 2 weeks post-SE. Radiotracer distribution was analyzed and statistical parametric mapping (SPM) was performed, as well as histological analysis of astroglial activation and neuronal cell loss. Atlas-based analysis of [18F]GE180 PET in rats revealed a dose-dependent regional decrease of TSPO expression at 2 weeks post-SE. Results of SPM analysis depicted a treatment effect already at 1 week post-SE in rats treated with the higher minocycline dose. In mice, TSPO PET imaging did not reveal any treatment effects whereas histology identified only a treatment-related reduction in dispersion of dentate gyrus neurons. TSPO PET served as an auspicious tool for temporal monitoring and quantification of anti-inflammatory effects during epileptogenesis. Importantly, the findings underline the need to applying more than one animal model to avoid missing treatment effects. For future studies, the setup is ready to be applied in combination with seizure monitoring to investigate the relationship between individual early treatment response and disease outcome. |
|---|---|
| ISSN: | 18787479 |
| DOI: | 10.1007/s13311-020-00834-5 |