Ablation of caspase-1 protects against TBI-induced pyroptosis in vitro and in vivo.
MouseTBIWeight-drop / impact-accelerationCaspase-1 deficient mice (Jackson Laboratories) and age-matched C57BL/6 wild-type; primary cortical neurons from embryonic day 14 BALB/c miceMalen = 18 mice per group; total animal number not statedIn vivo not applicable; in vitro added to culture mediumIn vivo none (genetic ablation). In vitro: VX-765 10 uM for…
Model: Weight-drop closed-skull contusion; a 200 g flat-ended steel weight dropped from 5 cm onto the left lateral skull producing moderate contusion of the left parietal cortex. In vitro: mechanical scratch, equiaxial stretch (12% strain, 1.0 Hz, 4 h) and LPS plus 5 mM ATP
Caspase-1 ablation reduced neurological deficits, cortical apoptosis, serum LDH, IFN-gamma and NLRP3 pathway signalling while raising TGF-beta and IL-10, and lowered caspase-1 activity, caspase-11 and GSDMD; in vitro caspase-1 siRNA and VX-765 similarly reduced neuronal apoptosis, LDH release and I…
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