In Vivo Brain Sampling Using a Microextraction Probe Reveals Metabolic Changes in Rodents after Deep Brain Stimulation

Brain
metabolomics is an emerging field that complements the more
traditional approaches of neuroscience. However, typical brain metabolomics
workflows require that animals be sacrificed and tend to involve tedious
sample preparation steps. Microdialysis, the standard technique to
study brain metabolites in vivo, is encumbered by significant limitations
in the analysis of hydrophobic metabolites, which are prone to adsorption
losses on microdialysis equipment. An alternative sampling method
suitable for in vivo brain studies is solid-phase microextraction
(SPME). In SPME, a small probe coated with a biocompatible polymer
is employed to extract/enrich analytes from biological matrices. In
this work, we report the use of SPME and liquid chromatography–mass
spectrometry for untargeted in vivo analysis of rodent’s brains
after deep brain stimulation (DBS). First, metabolite changes occurring
in brain hippocampi after application of 3 h of DBS to the animals’
prefrontal cortex were monitored with the proposed approach. As SPME
allows for nonlethal sampling, the same group of animals was sampled
again after 8 days of daily DBS therapy. After acute DBS, we detected
changes in a broad range of metabolites, including the amino acid
citrulline, which may reflect changes in nitric oxide production,
as well as various phospho- and glycosphingolipids. Measurements conducted
after chronic DBS showed a decrease in hippocampal corticosterone,
indicating that DBS may have a regulatory effect in the hypothalamic–pituitary–adrenal
axis. Our findings demonstrate the potential of in vivo SPME as a
tool of scientific and clinical interest capable of revealing changes
in a wide range of metabolites in brain tissue.