Development of In Vivo Imaging Tools for Investigating Astrocyte Activation in Epileptogenesis

• Published in: Molecular neurobiology 2018-05, Vol.55 (5), p.4463-4472
• Main Authors: Kostoula, Chrysavgi, Pascente, Rosaria, Ravizza, Teresa, McCown, Thomas, Schoch, Susanne, Vezzani, Annamaria, Becker, Albert J., van Loo, Karen M. J
• Format: Article
• Language: English
• Subjects: Animal models; Animals; Astrocytes; Astrocytes - metabolism; Astrocytes - pathology; Bioluminescence; Biomedical and Life Sciences; Biomedicine; Cell Biology; Epilepsy; Genes, Reporter; Glial fibrillary acidic protein; Glial Fibrillary Acidic Protein - genetics; Glial Fibrillary Acidic Protein - metabolism; Green Fluorescent Proteins - metabolism; Hippocampus - metabolism; Humans; IL-1β; Imaging, Three-Dimensional; Immunohistochemistry; Inflammation; Interleukin-1beta - genetics; Kainic Acid; Longitudinal studies; Luciferases - metabolism; Luminescent Measurements; Magnetic resonance imaging; Male; Mice; Mice, Inbred C57BL; Neurobiology; Neuroimaging; Neurology; Neurosciences; Phenotypes; Positron emission tomography; Promoter Regions, Genetic - genetics; RAW 264.7 Cells; Reporter gene; Rodents; Status Epilepticus - diagnostic imaging; Status Epilepticus - genetics; Status Epilepticus - pathology; Viruses
• ISSN: 0893-7648; 1559-1182
• DOI: 10.1007/s12035-017-0660-x

Insights into the dynamic changes in molecular processes occurring in the brain during epileptogenesis can substantially improve our understanding of their pathogenetic relevance. In this context, neuroinflammation is a potential mechanism of epileptogenesis which has recently been investigated in animal models by MRI or PET molecular imaging. Here, we developed an alternative and complementary molecular imaging strategy by designing a serotype 8 recombinant adeno-associated virus (AAV8) harboring promoter fragments of the GFAP or IL-1β promoter and a luciferase reporter gene. Mice were injected intrahippocampally with rAAV8 and treated with intracortical kainic acid to induce status epilepticus (SE) and hence epileptogenesis. In vivo bioluminescence imaging combined with immunohistochemistry revealed a significant activation of the GFAP promoter 24 h and 3 days after kainate-induced SE. For IL-1β, we identified the promoter region required for studying cell-specific induction of the promoter in longitudinal studies. We conclude that the GFAP promoter fragment represents a useful tool for monitoring the in vivo activation of astrocytes with an inflammatory phenotype during epileptogenesis, or under other pathophysiological conditions.