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Mit dieser Arbeit sollte die Auswirkung eines P-gp knockouts auf das Genom des Gehirns von Mäusen (P-gp „knockout“ Mäuse) im Alter von 3, 6, 9 sowie 12 Monaten im Vergleich zu Wildtyptieren untersucht werden. Die vorgelegte Arbeit konnte Hinweise auf einen unmittelbaren Zusammenhang zwischen P-gp knockout und neuronaler Dysfunktion geben. Dabei fanden sich insbesondere bei den jungen Tieren signifikante Unterschiede in der Expression von Genen, die für entzündliche Prozesse oder auch strukturelle und funktionelle Eigenschaften der verschiedenen Zellen des Gehirns eine wichtige Rolle spielen.
Postoperative Immune Suppression in Visceral Surgery: Characterisation of an Intestinal Mouse Model
(2011)
Background: Postoperatively acquired immune dysfunction is associated with a higher mortality rate in case of septic complications. As details of this severe clinical problem are still unknown, animal models are essential to characterise the mechanisms involved. Methods: Mice were laparotomised and the small intestine was pressed smoothly in antegrade direction. For extension of trauma, the intestine was manipulated three times consecutively. Following this, the ex vivo cytokine release of splenocytes was determined. The degree of surgical trauma was analysed by detection of HMGB1 and IL-6 in serum and by neutrophil staining in the muscularis mucosae. Results: We adapted the previously described animal model of intestinal manipulation to provide a model of surgically induced immune dysfunction. Following intestinal manipulation, the mice showed elevated serum levels of HMGB1 and IL-6 and increased infiltration of granulocytes into the muscularis mucosae. Ex vivo cytokine release by splenocytes was suppressed in the postoperative period. The degree of suppression correlated with the extent of surgical trauma. Conclusions: In this study, we describe a surgically induced immune dysfunction animal model, in which a significant surgical trauma is followed by an immune dysfunction. This model may be ideal for the characterisation of the postoperative immune dysfunction syndrome.