Modulation of the initial stages of systemic inflammation by intervention in the NFkB signalling pathway
| Autor: | Ângela Amaro-Leal |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: | |
| Zdroj: | Annals of Medicine, Vol 53, Iss sup1, Pp S5-S5 (2021) |
| Druh dokumentu: | article |
| ISSN: | 07853890 1365-2060 0785-3890 |
| DOI: | 10.1080/07853890.2021.1894004 |
| Popis: | AbstractSepsis is a systemic inflammatory state mediated by the innate immune system resulting in an excessive cellular response to severe infection, with high levels of morbidity and mortality. Furthermore, patients who survive sepsis, have long-term cognitive and functional impairment. Animal models are essential to clarify the pathophysiological mechanisms of sepsis. Herein, we characterise an animal model of lipopolysaccharide (LPS)-induced inflammation, evaluating neural and cardiac function, during the initial stages of infection. Male Wistar rats (12–20 wks, n = 24) were injected with LPS (E. coli serotype O127:B8; tail vein) and divided into 3 groups: LPS6 (6 mg/kg), LPS12 (12 mg/kg) and Sham (NaCl 0.9%; 0.1 ml/100g). At 6 and 24 h after LPS injection, an autonomic evaluation was performed in both conscious animals, with continuous radio-telemetry recording of blood pressure (BP) and heart rate (HR), and in anaesthetised animals (induction: sodium pentobarbital, 60 mg/kg, ip; maintenance: 20% solution, v/v) with BP, ECG, HR, tracheal pressure, respiratory frequency (RF) and body temperature continuously monitored. Baro and chemoreflex were evaluated with phenylephrine (0.2 ml, 25 µg/ml; iv) and lobeline (0.2 ml, 25 μg/ml; iv), respectively. Behavioural changes were also evaluated through the elevated-plus maze, open-field and Y-maze tests. Immunohistochemistry and RT-PCR were executed to determine heart and brain inflammatory state. Serum biomarkers levels for organ disfunction were also measured. Overall our results show a rise in BP and HR, and elevated RF due to increased chemoreflex sensitivity. 24 h following LPS injection, all groups have a significantly decreased baroreflex (p |
| Databáze: | Directory of Open Access Journals |
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