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Acute preoperative anti‐inflammatory treatment in a rat model for postoperative cognitive dysfunction; a role for the gut‐brain axis?
Author(s) -
Schoemaker Regien G.,
Hovens Iris B.,
Falcao Salles Joana G.,
Haan Jacco J.,
Leeuwen Barbara L.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.921.3
Subject(s) - neurogenesis , dentate gyrus , ibuprofen , hippocampus , medicine , morris water navigation task , microglia , hippocampal formation , open field , anesthesia , inflammation , psychology , neuroscience , pharmacology
Background Inflammation is considered a key factor in the development of post‐operative cognitive dysfunction (POCD). We hypothesize that acute preoperative anti‐inflammatory treatment with ibuprofen improves postoperative cognitive performance involving the gut‐brain axis in a rat‐model of POCD. Methods Male Wistar rats of 3 and 23 months old were fasted and received one preoperative bolus of ibuprofen (15 mg/kg i.p.) or handling without intervention as control, 30 minutes before being subjected to major abdominal surgery. Before and 7 days after intervention, fecal samples were collected to analyse the gut microbiome. Subsequently, rats were tested in the open field, novel object‐ and novel location recognition test and Morris water maze. Microglial morphology (IBA‐1) and neurogenesis (Double cortin) were assessed by immunohistochemistry after sacrifice at day 14. Results Ibuprofen treatment improved postoperative spatial memory but not spatial learning, and increased microglial activity and neurogenesis in the hippocampus. A principle coordinate analysis of the gut microbiome revealed a significant effect of age (p=0.001), no effect of Ibuprofen, but a significant interaction between these parameters (p =0.045). Microbiome richness appeared positively correlated to spatial learning, and negatively correlated to neurogenesis. Conclusion Our data indicate that preoperative ibuprofen treatment can selectively improve spatial memory. As this effect coincides with microglia activation and increased neurogenesis in the Dentate Gyrus of the hippocampus, we conclude that Ibuprofen may improve POCD by selectively interfering with hippocampal Dentate Gyrus function. Although gut microbiome parameters showed age‐, but not Ibuprofen‐related differences, associations with behavior and neurogenesis may support involvement of gut‐brain interactions in POCD. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .