Animal study demonstrates that pioglitazone reduces neuroinflammation and cognitive impairment in septic mice, indicating a protective role via PPAR-γ activation.
Key Points
To determine whether pioglitazone protects against sepsis-associated encephalopathy and to delineate the underlying PPAR-γ-dependent mechanisms.
Induced polymicrobial sepsis in male C57BL/6 mice using caecal ligation and puncture (CLP).
Administered pioglitazone with or without the PPAR-γ antagonist GW9662 at 24 hours post-CLP, assessing 14-day survival, neurobehavior, blood–brain barrier permeability, and hippocampal molecular markers.
Pioglitazone increased 14-day survival from 21.82% in untreated CLP mice to 46.15%, an effect abolished by GW9662 co-administration (19.36% survival).
Pioglitazone treatment improved learning and memory, preserved blood–brain barrier integrity by upregulating Claudin-5, and suppressed TLR4/NF-κB-driven cytokines (reducing TNF-α, IL-1β, and IL-6 while increasing IL-10) and neuronal apoptosis in a PPAR-γ-dependent manner.