Nonlinear Multimodal Imaging Characteristics of Early Septic Liver Injury in a Mouse Model of Peritonitis
Autor: | Nilay Köse-Vogel, Sven Stengel, Thomas Bocklitz, Hyeonsoo Bae, Melina Yarbakht, Jürgen Popp, Tobias Meyer, Michael Schmitt, Andreas Stallmach, Pranita Pradhan, Tony Bruns |
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Rok vydání: | 2019 |
Předmět: |
Male
Pathology medicine.medical_specialty Peritonitis Gene Expression 010402 general chemistry Immunofluorescence Spectrum Analysis Raman 01 natural sciences Multimodal Imaging Analytical Chemistry Sepsis Mice medicine Animals Humans RNA Messenger HMGB1 Protein Liver injury medicine.diagnostic_test Chemistry Abdominal Infection 010401 analytical chemistry Organ dysfunction Acute-phase protein Microtomy medicine.disease Immunohistochemistry 0104 chemical sciences Reverse transcription polymerase chain reaction Mice Inbred C57BL Disease Models Animal Microscopy Fluorescence Multiphoton Liver Cytokines medicine.symptom Acute-Phase Proteins |
Zdroj: | Analytical chemistry. 91(17) |
ISSN: | 1520-6882 |
Popis: | Sepsis constitutes a life-threatening organ failure caused by a deregulated host response to infection. Identifying early biomolecular indicators of organ dysfunction may improve clinical decision-making and outcome of patients. Herein we utilized label-free nonlinear multimodal imaging, combining coherent anti-Stokes Raman scattering (CARS), two-photon excited autofluorescence (TPEF), and second-harmonic generation (SHG) to investigate the consequences of early septic liver injury in a murine model of polymicrobial abdominal infection. Liver tissue sections from mice with and without abdominal sepsis were analyzed using multimodal nonlinear microscopy, immunofluorescence, immunohistochemistry, and quantitative reverse transcription polymerase chain reaction (qRT-PCR). Twenty-four hours after the induction of sepsis, hepatic mRNA of inflammatory cytokines and acute phase proteins was upregulated, and liver-infiltrating myeloid cells could be visualized alongside hepatocellular cytoplasmic translocation of high mobility group box 1. According to the statistical analysis based on texture feature extraction followed by the combination of dimension reduction and linear discriminant analysis, CARS (AUC = 0.93) and TPEF (AUC = 0.83) showed an excellent discrimination between liver sections from septic mice and sham-treated mice in contrast to SHG (AUC = 0.49). Spatial analysis revealed no major differences in the distribution of sepsis-associated changes between periportal and pericentral zones. These data suggest early alterations in hepatic lipid distribution and metabolism during liver injury and confirm nonlinear multimodal imaging as a promising complementary method for the real-time, label-free study of septic liver damage. |
Databáze: | OpenAIRE |
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