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Fig. 3 | Acta Neuropathologica Communications

Fig. 3

From: Persistent elevation of intrathecal pro-inflammatory cytokines leads to multiple sclerosis-like cortical demyelination and neurodegeneration

Fig. 3

Viral delivery of cytokines into the CSF caused microglial activation in the underlying cortex. Microglial activation, indicated by IBA1 reactivity, was widespread in all cortical layers and the corpus callosum at 28 days (illustrated for MOG immunised animals) post cytokine viral vector injection, whereas injection with eGFP vector led to minimal Iba1 expression that was not different from naïve rats (a,b). Subpial demyelinated lesions in animals immunised with MOG and injected with cytokine vectors were characterised by large numbers of Iba1+ microglia with a highly activated morphology at 28 dpi (c,d). No amoeboid-like macrophages could be seen in the GM parenchyma at any stage. The number of Iba1+ cells was significantly increased in the cortical layers of both IFA and MOG immunised cytokine vector injected animals in all regions and at all timepoints, except for the midline II-IV at 56 dpi (e,f), with the greatest increases seen in MOG immunised animals. The greatest increase in Iba1+ cells was seen in the midline layer I region, closest to the immune aggregates in the sagittal sulcus (e), with slightly lower numbers in midline layer II-V (e). Iba1+ numbers were higher in cortical layer I than underlying layer II-V (f). Data are presented as mean ± SEM. Statistics: one-way ANOVA with Tukey post-hoc test. **** P < 0.0001, * P < 0.05 naïve versus cytokine or ΔΔΔΔ P < 0.0001. ΔΔΔ P < 0.001, ΔΔ P < 0.01, Δ p < 0.05 for comparison between 28 and 56 dpi for the same group (IFA vs IFA). Scale bar = 200 μm (a,b), 25 μm (c,d)

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