Publication:

Attenuation and augmentation of ischaemia-related neuronal death by tumour necrosis factor-alpha in vitro (2000)

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

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

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.

Notes: 0953-816X (Print) Journal Article

  • Short Title: Attenuation and augmentation of ischaemia-related neuronal death by tumour necrosis factor-alpha in vitro
  • Date: 01-11-2000
  • Journal: European Journal of Neuroscience
  • Volume: 12
  • Issue: 11
  • Pages: 3863-3870
  • Publisher: Wiley-Blackwell Publishing Ltd.
  • Publication type: Article
  • Bibliographic status: Published

Keywords: Animals Benzoquinones/pharmacology Cell Death Free Radical Scavengers/pharmacology In Vitro Ischemic Attack, Transient/pathology/*physiopathology N-Methylaspartate/*toxicity NF-kappa B/metabolism Neurons/*drug effects/pathology/physiology Organ Culture Techniques Rats Rats, Wistar Receptors, Glutamate/physiology Superoxide Dismutase/genetics Superoxides/toxicity Time Factors Tumor Necrosis Factor-alpha/*pharmacology

Staff

Professor Derek Mann
Prof of Hepatology