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Title: The role of neuroinflammatory modulation on POCD development following surgery
Author: Rei Fidalgo, Antonio Manuel
ISNI:       0000 0004 2710 2082
Awarding Body: Imperial College London
Current Institution: Imperial College London
Date of Award: 2011
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The effects of peripheral surgery-induced inflammation and the role of the proinflammatory cytokine interleukin 1-beta (IL-1β) on cognitive function in mouse in several different contexts are explored. Lipopolysaccharide (LPS)-induced inflammation, but not isoflurane-induced anaesthesia, results in memory impairment in mouse, causing a permanent retrograde amnesia in contextual fear-conditioning tests. Blocking the action of IL-1β reduces the hippocampal memory deficit induced by LPS. Peripheral orthopaedic surgery results in inflammation in the brain and cognitive impairment in a mouse model of orthopaedic surgery. Such surgery is associated with increased levels of IL-1β in the serum and in the hippocampus. It also induces hippocampal microgliosis without being associated with an increase in apoptosis. Injection of an interleukin 1 receptor antagonist (IL1-ra) results in reduced microgliosis and reduced IL-1β levels in the serum and in the hippocampus. The inflammatory response to such surgical insult also results in impairment of remote (pre-frontal cortex (PFC)) localised memory in mouse as assessed by two tests of contextual remote memory. Such impairment is not accompanied by an increase in IL-1β in the PFC. There is also a reduction in the level of hippocampal brain derived neurotrophic factor (BDNF) which may contribute to the impairment of memory after such surgery. The murine anxiety response to peripheral orthopaedic surgery, as assessed using the social interaction test, shows that surgery does not increase anxiety in our animal model of peripheral surgery. Nor does such surgery affect olfactory memory under the conditions presented on the olfactory habituation-dishabituation task. A sub-pyrogenic dose of LPS alone fails to impair memory function. However, when the same is administered prior to peripheral surgery, it exacerbates surgery-induced cognitive dysfunction as assessed by fear-conditioning tests. It causes a concomitant additional increase in the levels of IL-1β in both plasma and hippocampus of those animals.
Supervisor: Ma, Daqing Sponsor: Fundação para a Ciência e Tecnologia
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral