4.6 Article

Peripheral Neutrophils-Derived Matrix Metallopeptidase-9 Induces Postoperative Cognitive Dysfunction in Aged Mice

Journal

FRONTIERS IN AGING NEUROSCIENCE
Volume 14, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fnagi.2022.683295

Keywords

matrix metallopeptidase-9; neutrophils; postoperative cognitive dysfunction; anesthesia and surgery; blood-brain barrier

Funding

  1. National Natural Science Foundation of China [81771133, 81970995]
  2. Shanghai Shenkang Hospital Development Center Founding [SHDC12017X11]
  3. Shanghai Municipal Science and Technology Commission Founding [21S31900100]
  4. Renji Hospital Clinical Innovation Foundation [PYII20-09, RJZZ18-019]
  5. Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Support [20191903]

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Aging is an important risk factor for postoperative cognitive dysfunction (POCD). This study found that peripheral neutrophils-derived matrix metalloproteinase-9 (MMP-9) contributes to POCD in aged mice by increasing blood-brain barrier permeability.
BackgroundAging is one of the most important risk factors of postoperative cognitive dysfunction (POCD); however, the mechanisms are still not completely understood. In this study, we explore the roles of matrix metalloproteinase-9 (MMP-9) in aged mice with POCD. MethodsAppendectomy was performed in 18-month-old C57BL/6 and MMP-9(-/-) mice under anesthesia to establish the POCD model. Learning and memory were assessed using the Morris water maze (MWM) or Barnes maze. Protein expression of MMP-9 was measured by Western blotting or enzyme-linked immunosorbent assay (ELISA). To explore the role of neutrophils-derived MMP-9 in POCD, we treated mice with anti-Gr-1 monoclonal antibody to deplete peripheral neutrophils. And the percentage of neutrophils and other leukocytes were detected by flow cytometry. We further used sodium fluorescein (NaFlu) to evaluate the blood-brain barrier (BBB) permeability. ResultsThe spatial learning and memory ability was injured, and expression of MMP-9 increased in both plasma and the hippocampus after anesthesia/surgery. However, cognitive dysfunction was alleviated in both MMP-9(-/-) and peripheral neutrophils-depleted mice. The permeability of BBB was increased after anesthesia/surgery while recused by anti-Gr-1 antibody administration. ConclusionThese findings suggest that peripheral neutrophils-derived MMP-9 could lead to POCD of aged mice through increasing the BBB permeability.

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