Fig. 5.

Immunohistochemical analysis of systemic TNF-α effects on prior pathology. Pathological examination was performed 18 h post-TNF-α (250 μg/kg) i.p in ME7 prion diseased mice 18 weeks post-inoculation. Labelling and quantification was performed for Synaptophysin × 5 (a–d, e), hyperphosphorylated Tau × 40 (f–i, j), the microglial marker IBA-1 × 40 (k-n, o), and apoptosis markers Caspase 3 × 100 (p, q) and TUNEL x 100 (q, r). Data were analysed using a one-way ANOVA followed by a Dunnett’s multiple comparison test. Statistical significance is denoted by ^∗(P < 0.05), ^∗∗∗(P < 0.001). All data are represented as the mean ± SEM, n = 3–5 for all groups. Additional hippocampal analysis was performed in ME7 animals 18 weeks post-inoculation; 18 h post i.p. saline or LPS (500 μg/kg). Animals were pretreated with either PBS or XPRO1595 (30 mg/kg). TUNEL positive cells were quantified in hippocampus (s) and data were analysed using two-way ANOVA followed by a Bonferroni multiple comparison test. Appropriate action of XPRO1595 (30 mg/kg) was verified by inhibition of TNF-α-induced (50 μg/kg) hypothermia in normal C57BL/6 mice (t). All data are represented as the mean ± SEM, n = 3–6 for all groups.