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Attenuation and augmentation of ischaemia-related neuronal death by tumour necrosis factor-alpha in vitro

Lookup NU author(s): Professor Derek Mann

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Abstract

Upregulation of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNF) occurs rapidly in the brain following ischaemia, although it is unclear whether this represents a neurotoxic or neuroprotective response. We have investigated whether TNF has different actions in the pre- and postischaemic periods in a tissue culture model of cerebral ischaemia. Organotypic hippocampal slice cultures were prepared from 8-10-day-old rats and maintained in vitro for 14 days. Neuronal damage was induced by either 1 h oxygen-glucose deprivation or 3 h exposure to NMDA or the superoxide generator duroquinone, and assessed after 24 h by propidium iodide fluorescence. TNF pretreatment was neuroprotective against both oxygen-glucose deprivation and duroquinone. This effect was associated with an activation of the transcription factor NFkappaB and upregulation of manganese superoxide dismutase, and was prevented by a free radical scavenger. When addition of TNF was delayed until the postinsult period, an exacerbation of neurotoxicity occurred, which was also prevented by a free radical scavenger. The actions of TNF are determined by whether TNF is present before or after an ischaemia-related insult. Both actions are mediated through the production of free radicals, and the response to TNF is determined by whether a cell is metabolically competent to respond by synthesis of antioxidant defences.


Publication metadata

Author(s): Mann DA; Wilde GJ; Pringle AK; Sundstrom LE; Iannotti F

Publication type: Article

Publication status: Published

Journal: European Journal of Neuroscience

Year: 2000

Volume: 12

Issue: 11

Pages: 3863-3870

ISSN (print): 0953-816X

ISSN (electronic): 1460-9568

Publisher: Wiley-Blackwell Publishing Ltd.

URL: http://dx.doi.org/10.1046/j.1460-9568.2000.00273.x

DOI: 10.1046/j.1460-9568.2000.00273.x

Notes: 0953-816X (Print) Journal Article


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