Ischemic and excitotoxic brain injury is enhanced in mice lacking the p55 tumor necrosis factor receptor

Devin S. Gary, Annadora J. Bruce-Keller, Mark S. Kindy, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Ischemic and excitotoxic insults to the brain induce rapid production of tumor necrosis factor-α (TNF), but the role of TNF in neuronal responses to brain injury are unclear. Two different TNF receptors (p55 and p75) are expressed in neurons and glia. To understand the role of TNF in brain injury, we generated mice that lack p55, p75, or both receptors. We report that neuronal damage after focal cerebral ischemia-reperfusion is significantly increased in mice lacking p55 receptors (85 ± 7 mm3 infarct volume; mean ± SD) compared with wild-type mice (70 ± 8 mm3) and mice lacking p75 receptors (72 ± 6 mm3). Moreover, mice lacking p55 receptors exhibited increased degeneration of CA3 hippocampal neurons after administration of the excitotoxin kainic acid compared with wild-type mice and mice lacking p75 receptors. When taken together with recent data showing that TNF can prevent apoptosis of cultured neurons exposed to oxidative and metabolic insults, our findings suggest that TNF plays a neuroprotective role after acute brain insults.

Original languageEnglish (US)
Pages (from-to)1283-1287
Number of pages5
JournalJournal of Cerebral Blood Flow and Metabolism
Volume18
Issue number12
DOIs
StatePublished - Dec 1998

Keywords

  • Epileptic seizures
  • Hippocampus
  • Kainic acid
  • Middle cerebral artery
  • Stroke

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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