Fig. 2.

NOX involvement in secondary TBI pathology. TBI induces activation of NOX enzymes (in particular, NOX1, NOX2, and NOX4) to produce ROS. The activated NOX induces secondary TBI pathology that can exacerbate the primary injury. A few prominent examples are depicted here: a. production of oxidative stress damage (peroxidation of lipids, oxidation of DNA, nitration of amino acids), b. generation of pro-inflammatory cytokines (IL-1β) by a TXNIP-mediated activation of NLRP3 inflammasome, and c. regulation of MG/MP phenotype towards the pro-inflammatory M1-like phenotype. Abbreviations: NLRP3 – nucleotide oligomerization domain (NOD)-like receptors containing Pyrin domain-3; TXNIP – thioredoxin interacting protein; LRR – leucine rich repeats; NAD – NACHT-associated domain; NACHT - domain present in NAIP, CIITA, HET-E and telomerase associated protein; PYD – pyrin domain; CARD – caspase recruitment domain; Cas – caspase-1; ASC - apoptosis associated speck-like protein containing a CARD; IL-1β – interleukin-1 beta; MG/MP – microglia/macrophage.