Interleukin-6 mediates delirium-like phenotypes in a murine model of urinary tract infection
| Autor: | Shouri Lahiri, S. Ananth Karumanchi, Gena Guidry, Faizan Anwar, Chandrakumar Bogguri, Mohammad H. Rashid, Haoming Pang, Nicklaus A. Sparrow, Ambart E. Covarrubias |
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| Rok vydání: | 2021 |
| Předmět: |
medicine.medical_specialty
Neurology UTI Urinary system Immunology Hippocampus urologic and male genital diseases Gastroenterology Pathogenesis Mice Cellular and Molecular Neuroscience Neuroinflammation Internal medicine medicine Animals Cognitive decline RC346-429 Maze Learning Interleukin 6 IL-6 Thigmotaxis biology Interleukin-6 business.industry Research General Neuroscience Delirium Antibodies Monoclonal Brain Neuron bacterial infections and mycoses female genital diseases and pregnancy complications Mice Inbred C57BL Disease Models Animal Phenotype IL-6 inhibition Urinary Tract Infections biology.protein Immunohistochemistry Female Neurology. Diseases of the nervous system business |
| Zdroj: | Journal of Neuroinflammation Journal of Neuroinflammation, Vol 18, Iss 1, Pp 1-16 (2021) |
| ISSN: | 1742-2094 |
| Popis: | BackgroundUrinary tract infection (UTI) is frequently implicated as a precipitant of delirium, which refers to an acute confusional state that is associated with high mortality, increased length of stay, and long-term cognitive decline. The pathogenesis of delirium is thought to involve cytokine-mediated neuronal dysfunction of the frontal cortex and hippocampus. We hypothesized that systemic IL-6 inhibition would mitigate delirium-like phenotypes in a mouse model of UTI.MethodsC57/BL6 mice were randomized to either: (1) non-UTI control, (2) UTI, and (3) UTI + anti-IL-6 antibody. UTI was induced by transurethral inoculation of 1 × 108Escherichia coli. Frontal cortex and hippocampus-mediated behaviors were evaluated using functional testing and corresponding structural changes were evaluated via quantification of neuronal cleaved caspase-3 (CC3) by immunohistochemistry and western blot. IL-6 in the brain and plasma were evaluated using immunohistochemistry, ELISA, and RT-PCR.ResultsCompared to non-UTI control mice, mice with UTI demonstrated significantly greater impairments in frontal and hippocampus-mediated behaviors, specifically increased thigmotaxis in Open Field (p p p p p r2 = 0.5087/p = 0.0028) and frontal IL-6 and CC3 (r2 = 0.2653,p ConclusionsThese data provide evidence for a role for IL-6 in mediating delirium-like phenotypes in a mouse model of UTI. These findings provide pre-clinical justification for clinical investigations of IL-6 inhibitors to treat UTI-induced delirium. |
| Databáze: | OpenAIRE |
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