In Vivo Solid‐Phase Microextraction for Sampling of Oxylipins in Brain of Awake, Moving Rats

Oxylipins are key lipid mediators of important brain processes, including pain, sleep, oxidative stress, and inflammation. For the first time, an in‐depth profile of up to 52 oxylipins can be obtained from the brains of awake moving animals using in vivo solid‐phase microextraction (SPME) chemical biopsy tool in combination with liquid chromatography–high resolution mass spectrometry. Among these, 23 oxylipins are detectable in the majority of healthy wildtype samples. This new approach successfully eliminates the changes in oxylipin concentrations routinely observed during the analysis of post‐mortem samples, allows time‐course monitoring of their concentrations with high spatial resolution in specific brain regions of interest, and can be performed using the same experimental set‐up as in vivo microdialysis (MD) thus providing a new and exciting tool in neuroscience and drug discovery. Biocompatible in vivo solid‐phase microextraction was used to measure 52 eicosanoids and other oxylipins directly in brains of awake moving rats with high temporal and spatial resolution. In vivo profiles of extracellular brain fluid did not reflect oxylipin concentrations in post‐mortem tissue and provide a novel tool to elucidate oxylipin pathways and function.