Netkova, M. (Mina) (2014) Deep or light? The effects of propofol anaesthesia and ischaemia on cerebral metabolism, brain inflammation and development of cognitive problems. thesis, Medicine.
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Abstract
Post-operative cognitive decline/dysfunction (POCD) is characterized by deterioration of cognitive function, and fluctuating mental status following anaesthesia and major cardiac and non-cardiac surgery, mainly in patients older than 65 years. We investigated the impact of dose of anaesthesia and hypoxic injury on cerebral metabolism, brain inflammation and the possible development of cognitive problems (such as POCD) in rat. We conducted a study to test the impact of deep propofol anaesthesia in rats on their cerebral metabolism (as assessed by an [18F] FDG PET scan) and tolerance to hypoxia (assessed by the Novel Object Recognition (NOR) behavioural test and by evaluate brain inflammation through an Iba-1 microglia staining). First, 19 male Wistar rats underwent either ‘deep’ or ‘light’ propofol anaesthesia, had a PET scan, and then were randomized to receive either ischaemia or no ischaemia. Then on day 4, they had the NOR test, and then on day 8 the rats were sacrificed. The brains were removed, rinsed and prepared for an immunohistochemistry analysis (Iba-1 staining for microglia). The PET scan analysis showed that deep propofol anaesthesia was associated with significantly lower [18F] FDG brain uptake than light propofol anaesthesia (39-53% lower, p<0.005 for all regions analyzed in the ROI-based analysis). The whole group of rats showed a significant preference (p < 0.001) for the novel object in the NOR test, but per group there were no significant differences. However, we observed a trend where the group of rats that received hypoxia spent less time exploring the objects (as percentage of the time they spent on other activities) compared to the group that did not receive ischaemia. The number of microglia cells did not differ significantly in any of the analyzed hippocampal areas per group (CA1, CA3, DG) with the Iba-1 analysis. There were no significant results in microglia activation between groups, however, we detected a trend of more microglia activation in the group that received light anaesthesia and no ischaemia in CA1 and CA3 regions of the hippocampus. In conclusion, deep propofol anaesthesia decreases cerebral metabolism in the whole brain and in some regions more than other compared to light propofol anaesthesia. Propofol anaesthesia might be protective to the brain by limiting microglia activation and preserving memory function. Although, most of our results are not significant, this research offers a new point of view and a strategy for a prospective study to gain a more complete picture of the interaction of anaesthesia, hypoxia, and external factors on cerebral metabolism, brain inflammation and cognition.
| Item Type: | Thesis (Thesis) |
|---|---|
| Supervisor name: | Kalmar, dr. A.F. and Absalom, Prof.dr. A.R. |
| Faculty: | Medical Sciences |
| Date Deposited: | 25 Jun 2020 11:04 |
| Last Modified: | 25 Jun 2020 11:04 |
| URI: | https://umcg.studenttheses.ub.rug.nl/id/eprint/2363 |
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