PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.
J, Z., P, W., N, L., & Y, G. (2026). PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.. CNS neuroscience & therapeutics. https://doi.org/10.1002/cns.71103
J Z, P W, N L, Y G. PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.. CNS neuroscience & therapeutics. 2026; doi: 10.1002/cns.71103
J Z, P W, N L, et al. PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.[J]. CNS neuroscience & therapeutics. 2026. DOI: 10.1002/cns.71103.
@article{j2026,
author = {Zhang J and Wang P and Li N and Gao Y},
title = {PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice.},
journal = {CNS neuroscience & therapeutics},
year = {2026},
doi = {10.1002/cns.71103},
note = {PMID: 42669896},
}
TY - JOUR AU - Zhang J AU - Wang P AU - Li N AU - Gao Y TI - PPARγ-Dependent Pioglitazone Treatment Suppresses Neuroinflammation and Improves Cognition in Sepsis-Associated Encephalopathy in Mice. T2 - CNS neuroscience & therapeutics PY - 2026 DO - 10.1002/cns.71103 AN - PMID:42669896 ER -
OBJECTIVE: To assess whether pioglitazone (Pio) protects against sepsis-associated encephalopathy (SAE) and to probe underlying mechanisms. METHODS: Sepsis was induced in male C57BL/6 mice by caecal ligation and puncture (CLP). At 24 h post-CLP, mice received Pio and/or the PPAR-γ antagonist GW9662 and were followed for 14-day survival. Cognitive and affective behaviors were evaluated using a behavioral battery. Blood-brain barrier (BBB) permeability was assessed by Evans blue extravasation, and hippocampal inflammatory and apoptotic readouts were examined by ELISA, immunoblotting, and TUNEL staining. RESULTS: CLP reduced 14-day survival to 21.82%, whereas Pio increased survival to 46.15%; GW9662 abolished this benefit (19.36%). Pio improved behavior consistent with reduced anxiety-like behavior and better learning/memory. Mechanistically, Pio decreased Evans blue leakage and increased Claudin-5, suppressed TLR4/NF-κB-associated inflammation (lower TNF-α, IL-1β, and IL-6; higher IL-10), and reduced neuronal apoptosis; these effects were largely reversed by GW9662. CONCLUSION: Pioglitazone alleviates sepsis-induced brain dysfunction and improves survival in mice in a PPAR-γ-dependent manner.