Figure 1
Theoretical depiction of pre-activation of the NLRP3 inflammasome in an obese person due to the increased presence of Danger Associated Molecular Proteins (DAMPs), such as amyloid beta, cholesterol and glucose7,8,10. Following severe TBI, NLRP3 genes are upregulated by 3 h post-injury. NLRP3, ASC, and caspase-1 mRNA are upregulated 6 h after severe TBI, while NLRP3 and caspase-1 mRNA continue to increase and peak by 7 days5. Protein expression for pro-caspase-1 and pro-IL-1β gradually increases up to 7 days5. Expression of these proteins releases caspase-1, IL-1β and IL-18 which lead to pyroptosis (i.e., inflammation-related neuronal cell death) and worse TBI outcomes3,4. IL-1β and IL-18 activate additional pro-inflammatory cytokines (i.e., IL-6, CRP), creating a positive feedback loop of inflammatory processes4.
