Fig. 1

The schematic for the proposed mechanism underlying the anti-neuroinflammatory effect of MC-tryptase inhibition. We propose that following ACA, MCs will be activated and degranulated leading to the release of MC-derived tryptase in the brain, which will activate microglial PAR-2. Phosphorylation and activation of p38 and activation of NFκB in response to activated PAR-2 will result in the release of microglia-derived proinflammatory cytokines, IL-6, and TNF-α. Resultantly, neuroinflammation will contribute to neurocognitive dysfunction following ACA. For this study, we used selective MC-tryptase inhibitor APC366 for treatment purposes while PAR-2 activator AC55541 and p-38 inhibitor SB203580 were used for intervention