Brain inflammation, neurodegeneration and seizure development following picornavirus infection markedly differ among virus and mouse strains and substrains
| Autor: | Ingo Gerhauser, Wolfgang Löscher, Wolfgang Baumgärtner, Sonja Bröer, Marion Bankstahl, Verena Haist, Lin Li, Muneeb Anjum, Christopher Käufer |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Picornavirus T-Lymphocytes viruses Hippocampus Epileptogenesis Virus Mice 03 medical and health sciences Epilepsy 0302 clinical medicine Species Specificity Developmental Neuroscience Seizures Theilovirus Interferon medicine Animals Encephalitis Viral Picornaviridae Infections Microglia biology Macrophages Body Weight Electroencephalography Neurodegenerative Diseases medicine.disease biology.organism_classification Virology Mice Inbred C57BL 030104 developmental biology medicine.anatomical_structure Neurology Immunology Female 030217 neurology & neurosurgery Encephalitis medicine.drug |
| Zdroj: | Experimental Neurology. 279:57-74 |
| ISSN: | 0014-4886 |
| Popis: | Infections, particularly those caused by viruses, are among the main causes of acquired epilepsy, but the mechanisms causing epileptogenesis are only poorly understood. As a consequence, no treatment exists for preventing epilepsy in patients at risk. Animal models are useful to study epileptogenesis after virus-induced encephalitis and how to interfere with this process, but most viruses that cause encephalitis in rodents are associated with high mortality, so that the processes leading to epilepsy cannot be investigated. Recently, intracerebral infection with Theiler's murine encephalomyelitis virus (TMEV) in C57BL/6 (B6) mice was reported to induce early seizures and epilepsy and it was proposed that the TMEV mouse model represents the first virus infection-driven animal model of epilepsy. In the present study, we characterized this model in two B6 substrains and seizure-resistant SJL/J mice by using three TMEV (sub)strains (BeAn-1, BeAn-2, DA). The idea behind this approach was to study what is and what is not necessary for development of acute and late seizures after brain infection in mice. Receiver operating characteristic (ROC) curve analysis was used to determine which virus-induced brain alterations are associated with seizure development. In B6 mice infected with different TMEV virus (sub)strains, the severity of hippocampal neurodegeneration, amount of MAC3-positive microglia/macrophages, and expression of the interferon-inducible antiviral effector ISG15 were almost perfect at discriminating seizing from non-seizing B6 mice, whereas T-lymphocyte brain infiltration was not found to be a crucial factor. However, intense microglia/macrophage activation and some hippocampal damage were also observed in SJL/J mice. Overall, the TMEV model provides a unique platform to study virus and host factors in ictogenesis and epileptogenesis. |
| Databáze: | OpenAIRE |
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