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

Nature Medicine volume 2, pages 788–794 (1996)Cite this article

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.

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Author information

Author notes

  1. Melissa K. Carpenter

    Present address: Cytotherapeutics, Inc., Two Richmond Square, Providence, Rhode Island, 02906, USA

Authors and Affiliations

  1. Sanders-Brown Research Center on Aging, University of Kentucky, 211 Sanders-Brown Building, Lexington, Kentucky, 40536–0230, USA

    Annadora J. Bruce, Warren Boling, Mark S. Kindy & Mark P. Mattson

  2. Department of Neurosurgery, University of Kentucky, Lexington, Kentucky, 40536, USA

    Warren Boling

  3. Department of Biochemistry, University of Kentucky, Lexington, Kentucky, 40536, USA

    Mark S. Kindy

  4. Immunex Corporation, 51 University Street, Seattle, Washington, 98101, USA

    Jacques Peschon & Melissa K. Carpenter

  5. Department of Psychology, University of Kentucky, Lexington, Kentucky, 40536, USA

    Philipp J. Kraemer

  6. Department of Biological Sciences, University of Kentucky, Lexington, Kentucky, 40536, USA

    Frederick W. Holtsberg

  7. Department of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky, 40536, USA

    Mark P. Mattson

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Bruce, A., Boling, W., Kindy, M. et al. Altered neuronal and microglial responses to excitotoxic and ischemic brain injury in mice lacking TNF receptors. Nat Med 2, 788–794 (1996). https://doi.org/10.1038/nm0796-788

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