Work

Irrigation fluid absorption induces metabolic and oxidative stress dysregulation activating NLRP3 and NF-κB pathways to drive hippocampal inflammatory responses

Year: 2026

Type: article

Abstract: Background: Irrigation fluid absorption during endoscopic procedures can lead to serious complications, but its effects on hippocampal function remain poorly understood. This study aimed to investigate the impact of irrigation fluid absorption on hippocampal metabolic homeostasis and inflammatory responses. Methods: Adult female Sprague-Dawley rats received intravenous 0.9% saline (control, 40 mL/kg, or 80 mL/kg) to simulate irrigation fluid absorption. Saline was infused over 30 min, and the animals were euthanized 15 min after cessation of anesthesia, corresponding to 45 min after initiation of the infusion. We assessed emergence time from anesthesia, hippocampal energy metabolism through targeted metabolomics, mitochondrial ultrastructure via transmission electron microscopy (TEM), oxidative stress markers, and NLRP3- and NF-κB-related inflammatory markers. Results: The 80 mL/kg group showed significantly prolonged anesthesia emergence time compared to controls (59.0 ± 13.5 vs. 31.7 ± 4.5 s; p < 0.01). Metabolomics revealed dose-dependent perturbations in the TCA cycle, glycolysis, and oxidative phosphorylation (p < 0.05). TEM analysis demonstrated severe mitochondrial ultrastructural damage in hippocampal neurons, including dose-dependent swelling, internal membrane disruption, and matrix dissolution. Both absorption groups showed altered glutathione redox status, characterized by increased GSSG levels and decreased GSH/GSSG ratios (p < 0.01), whereas SOD, CAT, MDA, NADPH, and GSH exhibited heterogeneous and non-linear changes across doses. At this early endpoint, increased NLRP3, P50/P65, IL-6, IL-18, and IL-33 immunoreactivity, together with decreased IκB immunoreactivity, indicated early changes in NLRP3- and NF-κB-related inflammatory signaling. Conclusion: Excessive irrigation fluid absorption induces hippocampal neuroinflammation through metabolic disturbance and redox dysregulation, which activates NLRP3 and NF-κB pathways. These findings suggest potential therapeutic targets for preventing neurological complications during endoscopic procedures.

Source: Frontiers in Pharmacology

DOI: 10.3389/fphar.2026.1881021