Fig. 5

Upstream nodal regulators for brain. This panel illustrates several of the top predicted upstream nodal regulators for brain from the IPA analysis of the genes for the + 1 pattern. On the left C vs T, the upstream regulators IL1β, IFNG, IL27, CSF2, TLR2, CD40, and CTNNB1 are illustrated along with the gene expression driving their predicted upregulation. As you can see, there is significant overlap in the gene expression driving these upstream regulators. The gene expression patterning is shown with cellular location; thus, you can see the relationship between the nuclear transcription factors that are driving expression of targets that impact inflammation and cellular proliferation. On the right side of the panel, C vs TE, is an illustration of how gene expression in these networks changes with exosome treatment. All of the inflammation-related regulators move from a predicted activation depicted by the orange color on the left panel to no change from control as indicated by the lack of color in the right panel. A number of the genes driving these changes such as MMP9, TIMP1, POMC, and PTX3 which show upregulation following TBI (red) show downregulation (green) following treatment with exosomes. This shows a powerful modulation of many of the gene expression patterns following exosome treatment. Not shown in this figure is the pattern for treatment with exosomes depleted of MALAT1 as this gene expression network is almost identical to that observed on the left with TBI treatment alone. The legend inserted on the top right describes the meaning of the various color assignments