Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors

Annadora J. Bruce, Warren Boling, Mark S. Kindy, Jacques Peschon, Philipp J. Kraemer, Melissa K. Carpenter, Frederick W. Holtsberg, Mark P. Mattson

Research output: Contribution to journalArticlepeer-review

Abstract

Brain injury, as occurs in stroke or head trauma, induces a dramatic increase in levels of tumor necrosis factor-α (TNF), but its role in brain injury response is unknown. We generated mice genetically deficient in TNF receptors (TNFR-KO) to determine the role of TNF in brain cell injury responses. Damage to neurons caused by focal cerebral ischemia and epileptic seizures was exacerbated in TNFR-KO mice, indicating that TNF serves a neuroprotective function. Oxidative stress was increased and levels of an antioxidant enzyme reduced in brain cells of TNFR-KO mice, indicating that TNF protects neurons by stimulating antioxidant pathways. Injury-induced microglial activation was suppressed in TNFR-KO mice, demonstrating a key role for TNF in injury-induced immune response. Drugs that target TNF signaling pathways may prove beneficial in treating stroke and traumatic brain injury.

Original languageEnglish (US)
Pages (from-to)788-794
Number of pages7
JournalNature Medicine
Volume2
Issue number7
DOIs
StatePublished - Jul 1996
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

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