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Conserved YKL-40 changes in mice and humans after postoperative delirium.

Publication ,  Journal Article
David-Bercholz, J; Acker, L; Caceres, AI; Wu, PY; Goenka, S; Franklin, NO; Rodriguiz, RM; Wetsel, WC; Devinney, M; Wright, MC; Zetterberg, H ...
Published in: Brain Behav Immun Health
December 2022

Delirium is a common postoperative neurologic complication among older adults. Despite its prevalence (14%-50%) and likely association with inflammation, the exact mechanisms that underpin postoperative delirium are unclear. This project aimed to characterize systemic and central nervous system (CNS) inflammatory changes following surgery in mice and humans. Matched plasma and cerebrospinal fluid (CSF) samples from the "Investigating Neuroinflammation Underlying Postoperative Brain Connectivity Changes, Postoperative Cognitive Dysfunction, Delirium in Older Adults" (INTUIT; NCT03273335) study were compared to murine endpoints. Delirium-like behavior was evaluated in aged mice using the 5-Choice Serial Reaction Time Test (5-CSRTT). Using a well established orthopedic surgical model in the FosTRAP reporter mouse we detected neuronal changes in the prefrontal cortex, an area implicated in attention, but notably not in the hippocampus. In aged mice, plasma interleukin-6 (IL-6), chitinase-3-like protein 1 (YKL-40), and neurofilament light chain (NfL) levels increased after orthopedic surgery, but hippocampal YKL-40 expression was decreased. Given the growing evidence for a YKL-40 role in delirium and other neurodegenerative conditions, we assayed human plasma and CSF samples. Plasma YKL-40 levels were similarly increased after surgery, with a trend toward a greater postoperative plasma YKL-40 increase in patients with delirium. However, YKL-40 levels in CSF decreased following surgery, which paralleled the findings in the mouse brain. Finally, we confirmed changes in the blood-brain barrier (BBB) as early as 9 h after surgery in mice, which warrants more detailed and acute evaluations of BBB integrity following surgery in humans. Together, these results provide a nuanced understanding of neuroimmune interactions underlying postoperative delirium in mice and humans, and highlight translational biomarkers to test potential cellular targets and mechanisms.

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Published In

Brain Behav Immun Health

DOI

EISSN

2666-3546

Publication Date

December 2022

Volume

26

Start / End Page

100555

Location

United States

Related Subject Headings

  • 3204 Immunology
  • 3202 Clinical sciences
 

Citation

APA
Chicago
ICMJE
MLA
NLM
David-Bercholz, J., Acker, L., Caceres, A. I., Wu, P. Y., Goenka, S., Franklin, N. O., … Terrando, N. (2022). Conserved YKL-40 changes in mice and humans after postoperative delirium. Brain Behav Immun Health, 26, 100555. https://doi.org/10.1016/j.bbih.2022.100555
David-Bercholz, Jennifer, Leah Acker, Ana I. Caceres, Pau Yen Wu, Saanvi Goenka, Nathan O. Franklin, Ramona M. Rodriguiz, et al. “Conserved YKL-40 changes in mice and humans after postoperative delirium.Brain Behav Immun Health 26 (December 2022): 100555. https://doi.org/10.1016/j.bbih.2022.100555.
David-Bercholz J, Acker L, Caceres AI, Wu PY, Goenka S, Franklin NO, et al. Conserved YKL-40 changes in mice and humans after postoperative delirium. Brain Behav Immun Health. 2022 Dec;26:100555.
David-Bercholz, Jennifer, et al. “Conserved YKL-40 changes in mice and humans after postoperative delirium.Brain Behav Immun Health, vol. 26, Dec. 2022, p. 100555. Pubmed, doi:10.1016/j.bbih.2022.100555.
David-Bercholz J, Acker L, Caceres AI, Wu PY, Goenka S, Franklin NO, Rodriguiz RM, Wetsel WC, Devinney M, Wright MC, Zetterberg H, Yang T, Berger M, Terrando N. Conserved YKL-40 changes in mice and humans after postoperative delirium. Brain Behav Immun Health. 2022 Dec;26:100555.

Published In

Brain Behav Immun Health

DOI

EISSN

2666-3546

Publication Date

December 2022

Volume

26

Start / End Page

100555

Location

United States

Related Subject Headings

  • 3204 Immunology
  • 3202 Clinical sciences