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Peripheral viral challenge triggers hippocampal production of inflammatory proteins

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Abstract

Peripheral viral infections increase seizure propensity and intensity in susceptible individuals. We have modeled this comorbidity by demonstrating that intraperitoneal (ip) injection of the conventional viral mimetic, polyinosinic-polycytidylic acid (PIC), renders the brain hypersusceptible to seizures induced by kainic acid (KA). At the molecular level, the hippocampus, which is the ictal site of KA-induced seizures, exhibits upregulated expression of messages encoding several inflammatory genes. Here, we profiled temporal expression of these genes at the protein level. Briefly, eight-week old female C57BL/6 mice were ip injected with 12 mg/kg of PIC and inflammatory proteins were quantified in the hippocampus and blood by ELISA. We found a robust but transient increase in blood concentration of IL-6, CXCL10, CCL2, CXCL9, CCL7 and CCL12 six hours after PIC challenge. CXCL1, IL1β, TNFα and CXCL2 featured a moderate increase. However, only four chemokines were increased in the hippocampus. CXCL10 showed the highest increase 6–12 h after PIC challenge, and its level dwindled to the baseline by 48 h. CXCL1, CXCl9 and CXCL2 were also transiently elevated but their maximal values were by an order of magnitude lower than the values for CXCL10. These results indicate that CXCL10 is the primary inflammatory protein generated in the hippocampus in response to PIC challenge, and that this chemokine may drive the development of seizure hypersusceptibility. In addition, the hippocampus featured a protracted increase in the levels of anaphylatoxins C3a and C5a, indicating the activation of the complement cascades.

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Acknowledgements

This study was supported by WVU Senate and WVU PSCOR grants. The content is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies.

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  1. Department of Neurobiology and Anatomy, West Virginia University School of Medicine, 4052 HSCN, P.O. Box 9128, Morgantown, WV, 26506-9128, USA

    Tiffany Petrisko & Gregory Konat

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  1. Tiffany Petrisko
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  2. Gregory Konat
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Correspondence to Gregory Konat.

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Petrisko, T., Konat, G. Peripheral viral challenge triggers hippocampal production of inflammatory proteins. Metab Brain Dis 32, 1249–1254 (2017). https://doi.org/10.1007/s11011-017-0030-4

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  • DOI: https://doi.org/10.1007/s11011-017-0030-4

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