Figure 5.

Microglial-derived TNF is neuroprotective through the TNF-p55 receptor. A, Toluidine blue staining of sections from BM-chimeric mice 24 h after pMCAo. B, Estimation of cortical infarct volume in BM-chimeric mice shows that KO-to-WT mice developed injuries similarly sized to those of WT-to-WT mice (p = 0.26, Mann–Whitney test; n = 15–20), showing that TNF produced by macrophages had no influence on tissue injury after ischemia. Furthermore, WT-to-KO mice developed injuries similarly sized to those of KO-to-KO mice (p = 0.38, Mann–Whitney test; n = 18), showing that macrophage-derived TNF could not compensate for the deficiency of microglial-derived TNF in KO mice and demonstrating a neuroprotective role of microglial-derived TNF. C, TNF staining of sections from ischemic BM-chimeric mice 24 h after pMCAo. TNF protein was present in all BM-chimeric mice, except in KO-to-KO BM-chimeric mice. D, Relative TNF mRNA levels in the ipsilateral, ischemic hemisphere 24 h after pMCAo from KO-to-WT, WT-to-WT, KO-to-KO, and WT-to-KO mice. TNF mRNA was present in KO-to-WT mice, WT-to-WT mice, and, to a lesser extent, in WT-to-KO mice, but not in KO-to-KO mice. Normalized mRNA levels were calibrated relative to a pool of cDNA from unmanipulated C57BL/6 control mice (n = 4–9). E, Toluidine blue staining of sections from TNF-p55R-KO (R1-KO), TNF-p75R-KO (R2-KO), TNF-p55p75R-KO (R-KO), and C57x129 mice 5 d after pMCAo. F, R1-KO mice developed significantly larger infarcts compared to both R2-KO and C57x129 mice but not to R-KO mice 5 d after pMCAo (one-way ANOVA followed by Dunn's multiple comparison test; n = 6–7). Results are expressed as mean ± SD. *p < 0.05; **p < 0.01; ***p < 0.001. Scale bars: A, E, 1 mm; C, 20 μm. IF, Infarct; ND, none detected.