2010
DOI: 10.1016/j.bbi.2010.04.004
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Systemic challenge with the TLR3 agonist poly I:C induces amplified IFNα/β and IL-1β responses in the diseased brain and exacerbates chronic neurodegeneration

Abstract: The role of inflammation in the progression of neurodegenerative disease remains unclear. We have shown that systemic bacterial insults accelerate disease progression in animals and in patients with Alzheimer’s disease. Disease exacerbation is associated with exaggerated CNS inflammatory responses to systemic inflammation mediated by microglia that become ‘primed’ by the underlying neurodegeneration. The impact of systemic viral insults on existing neurodegenerative disease has not been investigated. Polyinosi… Show more

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Cited by 188 publications
(164 citation statements)
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“…To mimic a response to viral rather than a bacterial infection, challenges with polyriboinosinicpolyribocytidilic acid (Poly I:C), a TLR-3 agonist and synthetic analogue of double-stranded RNA have been used in rats. Results have revealed an increase in the production of proinflammatory cytokines in the brain , an exacerbation of chronic neurodegeneration (Field et al, 2010), and an induction of nigrostriatal dopaminergic neurodegeneration in adult rats (Deleidi et al, 2010). When administered early in gestation to mice, acute poly I:C induced maternal immune activation and a subsequent increase in the numbers of dopaminergic neurons in the foetal brains during middle and late foetal development (Meyer et al, 2008a).…”
Section: Prenatal Systemic Infectionmentioning
confidence: 99%
“…To mimic a response to viral rather than a bacterial infection, challenges with polyriboinosinicpolyribocytidilic acid (Poly I:C), a TLR-3 agonist and synthetic analogue of double-stranded RNA have been used in rats. Results have revealed an increase in the production of proinflammatory cytokines in the brain , an exacerbation of chronic neurodegeneration (Field et al, 2010), and an induction of nigrostriatal dopaminergic neurodegeneration in adult rats (Deleidi et al, 2010). When administered early in gestation to mice, acute poly I:C induced maternal immune activation and a subsequent increase in the numbers of dopaminergic neurons in the foetal brains during middle and late foetal development (Meyer et al, 2008a).…”
Section: Prenatal Systemic Infectionmentioning
confidence: 99%
“…This physiological response is associated with neuroinflammation, especially type I IFN/ expression, within the brain. This neuroinflammatory response mimics the peripheral inflammatory response (Field et al, 2010). Poly I:C administration to mice induces a transient slight increase in core body temperature but a strong sickness behavioral response, assessed as a decrease in LMA and burrowing activity .…”
Section: Tlr3 Tlr7 Tlr8 and Tlr9: Nucleic Acidsmentioning
confidence: 99%
“…In the healthy adult brain, the signaling from the periphery to the brain is transient, and there is no evidence that it leads to tissue damage. In brains with ongoing chronic neurodegeneration, there is a growing body of evidence to show that the microglia are not only increased in number and have an activated phenotype, but appear to be "primed" by the ongoing pathology such that systemic inflammation leads to an exaggerated synthesis of pro-inflammatory cytokines Cunningham et al 2009;Field et al 2010). The switch in the microglia phenotype during systemic inflammation has been described in pre-clinical models of both acute (Palin et al 2008) and chronic (Cunningham et al 2005;Lunnon et al 2011) neurodegeneration.…”
Section: Systemic Inflammationmentioning
confidence: 99%