JNK-IN-8 treatment improves ARDS-induced cognitive impairment by inhibiting JNK/NF-κB-mediated NLRP3 inflammasome

Cognitive impairment is a critical complication of acute respiratory distress syndrome (ARDS), and effective interventions remain limited. Evidence suggests that c-Jun N-terminal kinase (JNK)-mediated neuroinflammation plays a significant role in the development of ARDS.

In this study, an in vivo rat model of ARDS was established using lipopolysaccharide treatment, and cognitive function was assessed through behavioral tests. The levels of pro-inflammatory cytokines, JNK, and the NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3) were measured by enzyme-linked immunosorbent assay, western blot, and immunohistochemical analysis.

Our results showed that treatment with the JNK inhibitor JNK-IN-8 alleviated cognitive impairment, reduced neuroinflammation, and suppressed NLRP3 inflammasome activation in the ARDS rat model. Additionally, the protective effect of JNK-IN-8 on cognitive function was blocked by nigericin, an NLRP3 activator, in an in vivo study.

These findings suggest that JNK-IN-8 improves ARDS-induced cognitive impairment by inhibiting the JNK/nuclear factor-κB-mediated activation of the NLRP3 inflammasome, highlighting a potential therapeutic approach for mitigating cognitive deficits in ARDS.