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

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. Access through your institution Buy or

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and amyloid β-peptide toxicity. _J. Neurochem._ 66, 869–872 (1996). CAS  PubMed  Google Scholar  Download references AUTHOR INFORMATION Author notes * Melissa K. Carpenter Present address:

Cytotherapeutics, Inc., Two Richmond Square, Providence, Rhode Island, 02906, USA AUTHORS AND AFFILIATIONS * 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 * Department of Neurosurgery, University of Kentucky, Lexington,

Kentucky, 40536, USA Warren Boling * Department of Biochemistry, University of Kentucky, Lexington, Kentucky, 40536, USA Mark S. Kindy * Immunex Corporation, 51 University Street, Seattle,

Washington, 98101, USA Jacques Peschon & Melissa K. Carpenter * Department of Psychology, University of Kentucky, Lexington, Kentucky, 40536, USA Philipp J. Kraemer * Department of

Biological Sciences, University of Kentucky, Lexington, Kentucky, 40536, USA Frederick W. Holtsberg * Department of Anatomy & Neurobiology, University of Kentucky, Lexington, Kentucky,

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ARTICLE CITE THIS ARTICLE 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 Download citation * Received: 22 March 1996 * Accepted: 10 May 1996 * Published: 01 July 1996 * Issue Date: 01 July 1996 * DOI:

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