MMP-9 inhibition alleviates postoperative cognitive dysfunction by improving glymphatic function via regulating AQP4 polarity

被引：7

作者：

Zhu, Binbin ^{[1
,2
]}

Cao, Angyang ^{[1
,2
]}

Chen, Chunqu ^{[1
,2
]}

Zhou, Weijian ^{[1
,2
]}

Luo, Wenjun ^{[1
,2
]}

Gui, Yu ^{[1
]}

Wang, Qinwen ^{[2
]}

Xu, Zhipeng ^{[1
]}

Wang, Jianhua ^{[1
,2
]}

机构：

[1] Ningbo Univ, Affiliated Hosp 1, Dept Hematol, Ningbo 315000, Peoples R China

[2] Ningbo Univ, Hlth Sci Ctr, Ningbo 315000, Peoples R China

来源：

INTERNATIONAL IMMUNOPHARMACOLOGY | 2024年 / 126卷

关键词：

AQP4; POCD; MMP-9; beta-DG; Polarity; PROVIDES NEUROPROTECTION; SURGERY; NEUROINFLAMMATION; IMPAIRMENT; ISCHEMIA;

D O I：

10.1016/j.intimp.2023.111215

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

Postoperative cognitive dysfunction (POCD) is a common complication after surgery, characterized by deficits in memory, attention and cognitive flexibility. However, the underlying mechanisms of POCD remain unclear. Neuroinflammation and blood-brain barrier disruption have been implicated as potential pathological processes. This study explores the neuroprotective effects and mechanisms of the matrix metalloproteinase(MMP-9)inhibitor GM6001 against POCD. We hypothesize GM6001 may reduce neuroinflammation and preserve blood- brain barrier integrity through direct inhibition of MMP-9. Moreover, GM6001 may stabilize aquaporin-4 polarity and glymphatic clearance function by modulating MMP-9-mediated cleavage of dystroglycan, a key protein for aquaporin-4 anchoring. Our results demonstrate GM6001 alleviates postoperative cognitive deficits and neuroinflammation. GM6001 also preserves blood-brain barrier integrity and rescues aquaporin-4 mislocalization after surgery. This study reveals a novel dual role for MMP-9 inhibition in cognitive protection through direct anti-neuroinflammatory effects and regulating aquaporin-4 membrane distribution. Targeting MMP-9 may represent a promising strategy to prevent postoperative cognitive dysfunction by integrating multiple protective mechanisms.

引用

页数：12