Microglia activation in acute and chronic neurodegeneration and the impact of systemic infection
Microglia activation in acute and chronic neurodegeneration and the impact of systemic infection
Microglia in the normal brain parenchyma are characterized by their downregulated or quiescent state. However, following almost any pathological insult to the brain they become activated and alter their morphology and upregulate their cell surface antigen expression. We have investigated the cytokine profile associated with acute and chronic neurodegeneration and microglia activation. We have shown that following acute injury to the brain, there is a period (24 h) of pro-inflammatory cytokine synthesis, but the microglia are morphologically activated for weeks. In murine prion disease pathology, a model of chronic neurodegeneration, the microglia are significantly increased in number and are morphologically activated. However, the cytokine profile is anti-inflammatory and dominated by TGFb. However, these activated microglia are primed, as a systemic challenge with endotoxin, to mimic a peripheral infection leads to enhanced cytokine synthesis and exaggerated behavioural sequelae. Interactions between systemic inflammation and an ongoing inflammatory response in the brain is relevant to many acute and chronic neurodegenerative conditions in human beings.
cytokines, endotoxin, macrophage, microglia, neurodegeneration
p.33
Perry, V.Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
December 2003
Perry, V.Hugh
8f29d36a-8e1f-4082-8700-09483bbaeae4
Perry, V.Hugh
(2003)
Microglia activation in acute and chronic neurodegeneration and the impact of systemic infection.
Journal of Neurochemistry, 87 (s1), .
(doi:10.1046/j.1474-1644.2003.2173_10.x).
Abstract
Microglia in the normal brain parenchyma are characterized by their downregulated or quiescent state. However, following almost any pathological insult to the brain they become activated and alter their morphology and upregulate their cell surface antigen expression. We have investigated the cytokine profile associated with acute and chronic neurodegeneration and microglia activation. We have shown that following acute injury to the brain, there is a period (24 h) of pro-inflammatory cytokine synthesis, but the microglia are morphologically activated for weeks. In murine prion disease pathology, a model of chronic neurodegeneration, the microglia are significantly increased in number and are morphologically activated. However, the cytokine profile is anti-inflammatory and dominated by TGFb. However, these activated microglia are primed, as a systemic challenge with endotoxin, to mimic a peripheral infection leads to enhanced cytokine synthesis and exaggerated behavioural sequelae. Interactions between systemic inflammation and an ongoing inflammatory response in the brain is relevant to many acute and chronic neurodegenerative conditions in human beings.
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Published date: December 2003
Keywords:
cytokines, endotoxin, macrophage, microglia, neurodegeneration
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Local EPrints ID: 55959
URI: http://eprints.soton.ac.uk/id/eprint/55959
ISSN: 0022-3042
PURE UUID: 79cbc711-9b10-42fa-9363-c382734939ce
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Date deposited: 07 Aug 2008
Last modified: 15 Mar 2024 10:58
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