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Title: Identifying the preventive cellular mechanisms of memory decline after surgery
Author: Vizcaychipi, Marcela Paola
ISNI:       0000 0004 2743 6680
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2012
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Memory and cognitive decline following surgery pose a major threat to the ageing population. Postoperative memory decline (POCD) has potentially devastating consequences due to its detrimental effects on quality of life and increased level of dependence. Acute neuroinflammatory changes after non-neurosurgical procedures have been linked to memory decline. Inflammation is the reflection of ongoing intracellular processes precipitated by stress following major insults such as surgery. I hypothesised that POCD is caused by an imbalance of cytoprotective mechanisms secondary to an inadequate physiological response to physiological stress. I set out to identify: 1) how memory is impaired in murine surgical models, using wild type and two genetically modified mouse lines, involving membrane danger receptors, purinergic receptor, ion gated channel 7 (P2X7) gene knockouts and the cytoplasmic chaperone heat shockprotein-72 (Hsp72), Hsp72 overexpressors, and 20 the effect of xenon anaesthesia and atorvastatin on memory decline following surgery. The inflammatory response was modelled by using multivariable analysis software (SIMCA) to identify a physiological signature, and the flow cytometry (FACS) technique of multiple cell-type responses within the hippocampus was optimised. The lack of P2X7 receptors could not prevent the development of POCD after tibial facture surgery under general anaesthesia. Over expression of Hsp72 proved to prevent POCD and its effect was associated with reduced microglia activation. Pretreatment with xenon and atorvastatin also prevented the development of POCD. In conclusion, SIMCA and FACS are potentially useful complementary methods for assessment of inflammation. P2X7 could not be proven to be involved in the development of POCD while the role of Hsp72 in POCD was proved and the prevention of POCD by using xenon through this mechanisms and atorvastatin by ameliorating the inflammatory response.
Supervisor: Maze, Mervyn ; Palazzo, Mark ; Ma, Daqing Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral