1. In-depth characterization of the neuroinflammatory reaction induced by peripheral surgery in an animal model.
- Author
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Plaschke K, Schulz S, Rullof R, Weigand MA, and Kopitz J
- Subjects
- Acetylcholine cerebrospinal fluid, Animals, Brain drug effects, Chemokines biosynthesis, Chemokines cerebrospinal fluid, Chemokines genetics, Cholinesterase Inhibitors pharmacology, Cytokines biosynthesis, Cytokines cerebrospinal fluid, Cytokines genetics, Delirium etiology, Encephalitis genetics, Encephalitis prevention & control, Gene Expression Profiling, Gene Expression Regulation drug effects, Hepatectomy adverse effects, Intraoperative Complications cerebrospinal fluid, Intraoperative Complications prevention & control, Male, Mice, Models, Animal, Physostigmine pharmacology, Postoperative Complications cerebrospinal fluid, Postoperative Complications prevention & control, Rats, Rats, Wistar, Acetylcholine metabolism, Brain metabolism, Cholinesterase Inhibitors therapeutic use, Encephalitis etiology, Intraoperative Complications etiology, Physostigmine therapeutic use, Postoperative Complications etiology
- Abstract
Delirium is a common complication seen after surgery and anesthesia, in particular in older patients. Although the etiology of postoperative delirium is only incompletely understood, various lines of evidence suggest that proinflammatory signaling from the peripheral site of inflammation to central nervous system results in a decrease of cerebral acetylcholine (ACh) levels thereby inducing neuroinflammation. To corroborate this theory, we applied an animal model for characterization of the neuroinflammatory response after partial hepatectomy (HPx). In this model, the surgery-induced decrease in cerebral ACh levels can be prevented by intraoperative application of physostigmine. Thus, ACh-associated changes in the expression and secretion of inflammation-related compounds can be assessed by comparing the results obtained after surgery, in physostigmine-treated and untreated controls. This way we were able to show that the decrease of cerebral ACh triggers increased secretion of IL-1β, IL-6, TNFα, MIP-2 (CCL3), RANTES, MCP1, IFNgamma, and IP-10. A gene array covering the expression of 370 inflammation-related genes indicated 13 candidates that are induced upon cerebral ACh decrease after HPx. Quantification of the changes in the expression of these candidates by the comparative C
T method revealed a significant increase (> 1.5-fold) in the expression of IL-1β, IL-6, TNFα, MIP2, RANTES, MCP1, TLR2, TLR4, HMGB1, TNFSF6, TNFSF12, IL1R1 and ILR6. Thus, our results suggest that peripheral surgery induces a reduction of cerebral ACh levels which trigger a complex neuroinflammatory response. From a clinical point of view, manipulating cerebral ACh levels by procholinergic drugs such as physostigmine could become an option to therapeutically target this kind of neuroinflammation.- Published
- 2018
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