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Palmitoylethanolamide ameliorates postoperative cognitive dysfunction via microglial PPARα-mediated anti-inflammatory and neuroprotective mechanisms

Xiaojun Zhang, Wensi Wu, Zhenzhen Zheng, Guijie Liu, Dongliang Li, Liang Li. Exp Neurol. 2026 May:399:115664.

Laboratory studyOther animals

Design
Laboratory study
Subjects
Aged mice, using an aged-mouse model of postoperative cognitive dysfunction; additional in vitro microglial experiments
Dose used in the study
Not stated in the abstract
Duration
Not stated in the abstract
What was measured
Cognitive performance (open field test, novel object recognition, Barnes maze); neuroinflammation, microglial activation, neuronal integrity and synaptic plasticity markers; the role of PPAR-alpha via shPPAR-alpha knockdown in prefrontal cortex microglia

What the authors reported

PEA improved short- and long-term memory in aged mice with postoperative cognitive dysfunction. It reduced microglial activation, shifted microglia toward an anti-inflammatory phenotype, preserved neurons and increased synaptic plasticity proteins. These effects depended on PPAR-alpha: knocking down PPAR-alpha in prefrontal cortex microglia abolished them.

Limits of this study

An aged-mouse model study with combined in vitro work; it cannot show effect in people undergoing surgery. The authors declare no competing interests.

Source

PubMed 41577115 · doi:10.1016/j.expneurol.2026.115664

Entry checked against the abstract on PubMed on 2026-09-22. The dose shown is the dose the researchers used. It is not a recommendation. How to read this page.