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Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration

Palin, Karine, Cunningham, Colm, Forse, Penny, Perry, V. Hugh and Platt, Nick (2008) Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration Neurobiology of Disease, 30, (1), pp. 19-29. (doi:10.1016/j.nbd.2007.11.012). (PMID:18255301).

Record type: Article


Axon loss in the CNS is characteristic of many neurodegenerative diseases but the mechanisms of axon degeneration are poorly understood. In particular, we know little of the inflammatory response triggered by CNS axon degeneration with comparison to that provoked by death of the neuronal cell body. We show that Wallerian degeneration of the mouse optic nerve induces transcription of TGF-?1 and TNF-?, but not pro-inflammatory cytokines IL-1? and IL-6 and microglial activation. This atypical inflammatory response resembles macrophages that have phagocytosed apoptotic cells and prion-infected CNS. Significantly, peripheral endotoxin challenge after injury switched this profile by inducing IL-1?, IL-6 transcripts, other inflammation-associated products and reducing neurofilament immunoreactivity. We propose that microglia are activated by Wallerian degeneration and persist in an atypical but “primed” state and can be switched by systemic inflammation to provoke a classical pro-inflammatory profile with potentially deleterious consequences.

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e-pub ahead of print date: 23 December 2007
Published date: April 2008
Keywords: axon, neurodegeneration, microglia, lipopolysaccharide


Local EPrints ID: 56030
ISSN: 0969-9961
PURE UUID: ed7b9550-2167-4ebc-8c47-fa0a8673906e

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Date deposited: 21 Aug 2008
Last modified: 17 Jul 2017 14:31

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Author: Karine Palin
Author: Colm Cunningham
Author: Penny Forse
Author: V. Hugh Perry
Author: Nick Platt

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