Open AccessTumor Necrosis Factor α is Reparative via TNFR1 in the Hippocampus and via TNFR2 in the Striatum after Virus‐Induced Encephalitis
Author(s) -
Rodriguez Moses,
Zoecklein Laurie,
Papke Louisa,
Gamez Jeff,
Denic Aleksandar,
Macura Slobodan,
Howe Charles
Publication year - 2009
Publication title -
brain pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.986
H-Index - 132
eISSN - 1750-3639
pISSN - 1015-6305
DOI - 10.1111/j.1750-3639.2008.00151.x
Subject(s) - hippocampal formation , tumor necrosis factor alpha , hippocampus , striatum , pathology , necrosis , encephalitis , biology , microglia , parenchyma , medicine , inflammation , immunology , virus , endocrinology , dopamine
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.