Tumor necrosis factor α is reparative via TNFR1 in the hippocampus and via TNFR2 in the striatum after virus-induced encephalitis

Moses Rodriguez, Laurie Zoecklein, Louisa Papke, Jeff Gamez, Aleksandar Denic, Slobodan Macura, Charles Howe

Research output: Contribution to journalArticlepeer-review

19 Scopus citations

Abstract

Differentiating between injurious and reparative factors facilitates appropriate therapeutic intervention. We evaluated the role of tumor necrosis factor α (TNFα) in parenchymal brain pathology resolution following virus-induced encephalitis from a picornavirus, Theiler's murine encephalomyelitis virus (TMEV). We infected the following animals with TMEV for 7 to 270 days: B6/129 TNF-/- mice (without TNFα expression), B6/129 TNFR1-/- mice (without TNFα receptor 1 expression), and B6/129 TNFR2-/- mice (without TNFα receptor 2 expression). Normal TNFα-expressing controls were TMEV-infected B6, 129/J, B6/129F1 and B6/129F2 mice. Whereas all strains developed inflammation and neuronal injury in the hippocampus and striatum 7 to 21 days postinfection (dpi), the control mice resolved the pathology by 45 to 90 dpi. However, parenchymal hippocampal and striatal injury persisted in B6/129 TNF-/- mice following infection. Treating virus-infected mice with active recombinant mouse TNFα resulted in less hippocampal and striatal pathology, whereas TNFα-neutralizing treatment worsened pathology. T1 "black holes" appeared on MRI during early infection in the hippocampus and striatum in all mice but persisted only in TNF-/- mice. TNFR1 mediated hippocampal pathology resolution whereas TNFR2 mediated striatal healing. These findings indicate the role of TNFα in resolution of sublethal hippocampal and striatal injury.

Original languageEnglish (US)
Pages (from-to)12-26
Number of pages15
JournalBrain Pathology
Volume19
Issue number1
DOIs
StatePublished - Jan 2009

Keywords

  • Cytokine
  • Neuroinflammation
  • Neuropathology
  • Neuroprotection
  • Theiler's murine encephalomyelitis virus
  • Virus persistence

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neuroscience(all)
  • Clinical Neurology

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