ORIGINAL RESEARCH article
Front. Immunol.
Sec. Inflammation
Volume 16 - 2025 | doi: 10.3389/fimmu.2025.1650254
The critical role of matrix metalloproteinase 9-mediated microglial polarization in perioperative neurocognitive disorders of aged rats
Provisionally accepted
Xi Xin1,2,3,4,5
Haonan Zhang1,2,3,4,5
Chenyi Yang2,3,4,5,6Xinyi Wang2,3,4,5,6Lin Zhang1,2,3,4,5Ji Ma1,2,3,4,5
Haiyun Wang1,2,3,4,5,6,7*- 1The Third Central Clinical College of Tianjin Medical University, Tianjin, China
- 2Tianjin Third Central Hospital, Tianjin, China
- 3Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin, China
- 4Artificial Cell Engineering Technology Research Center, Tianjin, China
- 5Tianjin University Central Hospital, Tianjin, China
- 6Nankai University, Tianjin, China
- 7Nankai University Affinity the Third Central Hospital, Tianjin, China
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Perioperative neurocognitive disorders (PND) is a significant clinical syndrome and neuroinflammation is an important pathological process. Matrix metalloproteinase 9 (MMP9) as a Zn2+-dependent matrix enzyme, not only maintains the integrity of the blood-brain barrier and synaptic plasticity, but also plays a key regulatory factor in peripheral and central nervous inflammation. This study aimed to investigate the effects of MMP9-mediated microglial polarization on surgery-induced neuroinflammation in aged rats and to provide novel targets for prevention and treatment of PND. This study utilized an intraperitoneal injection of SB-3CT, an MMP9 inhibitor, to impede the action of MMP9. Morris water maze and novel object recognition test were conducted to assess behavioral performances. Western blot was employed to examine hippocampal inflammatory factors. Immunofuorescence and flow cytometry were used to examine the transformation of microglia phenotype. The findings demonstrated that surgical intervention induced significant impairment in learning and memory performance in aged rats, accompanied by elevated MMP9 expression, exacerbated hippocampal inflammation, and microglial polarization characterized by a predominant M1 phenotype. Administration of SB-3CT effectively reversed these pathological manifestations. Consequently, the inhibition of MMP9 can enhance neurological function by modulating the polarization of microglia and alleviating neuroinflammation, which is a new approach for perioperative neuroprotection in high-risk PND patients.
Keywords: Neuroinflammation, Matrix Metalloproteinase 9, Perioperative neurocognitive disorders, Microglia, Aged
Received: 19 Jun 2025; Accepted: 04 Aug 2025.
Copyright: © 2025 Xin, Zhang, Yang, Wang, Zhang, Ma and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Haiyun Wang, The Third Central Clinical College of Tianjin Medical University, Tianjin, China
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