Figure 4.

Gene array analyses of the impact of concussive (30 g weight drop) mTBI (versus uninjured controls) on the hippocampus of animals derived from Figure 3, and the ameliorative effects of Ex-4 administration. (A) Pathway analysis: the effects of mild TBI (mTBI) vs. sham on the 10 most down-regulated (green) and up-regulated (red) pathway gene sets in mouse hippocampus are shown (pathway Z-scores are presented). The effects of treatment of mTBI with Ex-4 are shown in the black bars. In these black bars Ex-4 treatment of mTBI induced a change in gene sets relative to the mTBI group. Where no black bar is present, Ex-4 had no effect on gene sets relative to mTBI. In large part, treatment with Ex-4 prevented the down-regulation of the 10 most affected pathways associated with mTBI, while Ex-4 treatment had beneficial effects upon three of 10 up-regulated pathways.

(B) Selecting the ‘Alzheimers disease dn’ pathway as a representative of those whose changes induced by mTBI were ameliorated by Ex-4, the pathway is opened to reveal the individual genes that comprise it (whose gene identities are shown as their gene symbol), presented as a classic heat map: up-regulation (red) and down-regulation (green). Remarkably, across the majority of individual genes mTBI-induced up-regulation is countered by Ex-4 mitigation. APP up-regulation by mTBI is noted, in line with TBI providing a conduit towards AD, which is mitigated by Ex-4. The scale for expression level is shown on the upper right, and the group comparisons are shown at the bottom of each section on the heat map. Adapted from Tweedie et al., [162].