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. 2021 Feb 4;11(1):3047.
doi: 10.1038/s41598-021-82606-5.

Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults

Niccolò Terrando #  1 , John J Park #  2 , Michael Devinney #  1 , Cliburn Chan  1 , Mary Cooter  1 , Pallavi Avasarala  1 , Joseph P Mathew  1 , Quintin J Quinones  1 , Krishna Rao Maddipati  3 , Miles Berger  4 ; MADCO-PC Study Team
Collaborators, Affiliations

Immunomodulatory lipid mediator profiling of cerebrospinal fluid following surgery in older adults

Niccolò Terrando et al. Sci Rep. .

Abstract

Arachidonic acid (AA), docosahexaenoic acid (DHA), and eicosapentaenoic acid (EPA) derived lipids play key roles in initiating and resolving inflammation. Neuro-inflammation is thought to play a causal role in perioperative neurocognitive disorders, yet the role of these lipids in the human central nervous system in such disorders is unclear. Here we used liquid chromatography-mass spectrometry to quantify AA, DHA, and EPA derived lipid levels in non-centrifuged cerebrospinal fluid (CSF), centrifuged CSF pellets, and centrifuged CSF supernatants of older adults obtained before, 24 h and 6 weeks after surgery. GAGE analysis was used to determine AA, DHA and EPA metabolite pathway changes over time. Lipid mediators derived from AA, DHA and EPA were detected in all sample types. Postoperative lipid mediator changes were not significant in non-centrifuged CSF (p > 0.05 for all three pathways). The AA metabolite pathway showed significant changes in centrifuged CSF pellets and supernatants from before to 24 h after surgery (p = 0.0000247, p = 0.0155 respectively), from before to 6 weeks after surgery (p = 0.0000497, p = 0.0155, respectively), and from 24 h to 6 weeks after surgery (p = 0.0000499, p = 0.00363, respectively). These findings indicate that AA, DHA, and EPA derived lipids are detectable in human CSF, and the AA metabolite pathway shows postoperative changes in centrifuged CSF pellets and supernatants.

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Conflict of interest statement

The authors in the present study declare no competing interests. MB has received material support (i.e., electroencephalogram monitors) from Masimo, Inc (Irvine, CA, USA) for a postoperative recovery study in older adults and has attended Masimo Consulting Sessions (for which his $1000 honorarium was donated at his request to the Foundation for Anesthesia Education & Research). Dr Berger has also received legal consulting fees related to perioperative neurocognitive disorders. Niccolò Terrando is a member of the Editorial Board (Neuroscience) of Scientific Report.

Figures

Figure 1
Figure 1
Centrifuged CSF Pellet and Supernatant median log concentrations of lipid mediators over time (N = 20). As supernatant analyte concentrations tended to be lower than pellet analyte concentrations by a few orders of magnitude, a log scale was used to present both sample types. *Indicates a significant (p < 0.05) effect of sample type on analyte concentration. **Indicates a significant (p < 0.05) effect of both time, and time by sample type interaction for analyte concentration. (A) PGE2. (B) LXA4. (C) 5(S),12(S)-DiHETE. (D) 5-HETE. (E) 15-HETE. (F) 12-HETE. (G) 11-HETE. (H) 4-HDoHE. (I) 13-HDoHE.
Figure 2
Figure 2
Non-centrifuged CSF heatmaps for AA, DHA, and EPA derived metabolite pathway changes from pre-op to 6 weeks post-op (N = 72). Patients are listed as numbers on the x-axis for each heatmap. Heatmap scale numbers represent natural log ratios of analyte concentrations from pre-op to 6 weeks post-op.
Figure 3
Figure 3
Centrifuged CSF cell pellet heatmaps for AA, DHA, and EPA derived metabolite pathway changes from pre-op to 6 weeks post-op (N = 20). Patients are listed as numbers on the x-axis for each heatmap. Heatmap scale numbers represent natural log ratios of analyte concentrations from pre-op to 6 weeks post-op.
Figure 4
Figure 4
Centrifuged CSF supernatant heatmaps for AA, DHA, and EPA derived metabolite pathway changes from pre-op to 6 weeks post-op (N = 20). Patients are listed as numbers on the x-axis for each heatmap. Heatmap scale numbers represent natural log ratios of analyte concentrations from pre-op to 6 weeks post-op.
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