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Microglia Activation, the Core Process in Neuroinflammation?

X-rayNeuroinflammation is a brain immune response that is associated with neurodegenerative diseases, and is primarily driven by activation of microglia, the brain’s resident macrophages. Dysregulation in peripheral and central inflammatory cytokine signaling interrupts normal microglial function, leading to neuronal dysfunction, neurotoxicity, neurodegeneration , and attenuated neurogenesis, processes that underlie most CNS diseases and result in deleterious effect on behavior, mood, motivation and cognition. Researchers measured the neuroinflammatory response produced by a systemic administration of the Escherichia coli lipopolysaccharide (LPS: endotoxin) in eight healthy male subjects with the PET radiotracer [11C]PBR28 which binds to translocator protein, a molecular marker that is up-regulated by microglial activation. They also measured inflammatory cytokines in serum and sickness behavior profiles before and after LPS administration to relate brain microglial activation with systemic inflammation and behavior. LPS administration significantly increased [11C]PBR28 binding 30-60%, demonstrating microglial activation throughout the brain, which was accompanied by an increase in blood levels of inflammatory cytokines, vital sign changes, and sickness symptoms. This is believed to be the first demonstration in humans that a systemic LPS challenge induces robust increases in microglial activation in the brain. 

Sandiego, CM, et al. Imaging robust microglial activation after lipopolysaccharide administration in humans with PET. PNAS, October 6, 2015, vol. 112, no. 40

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