The role of neuroinflammatory modulation on POCD development following surgery
Author(s)
Rei Fidalgo, Antonio Manuel
Type
Thesis or dissertation
Abstract
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.
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.
Date Issued
2011
Date Awarded
2011-11
Advisor
Ma, Daqing
Sponsor
Fundação para a Ciência e Tecnologia
Creator
Rei Fidalgo, Antonio Manuel
Publisher Department
Surgery and Cancer
Publisher Institution
Imperial College London
Qualification Level
Doctoral
Qualification Name
Doctor of Philosophy (PhD)