Edaravone Maintains AQP4 Polarity Via OS/MMP9/β-DG Pathway in an Experimental Intracerebral Hemorrhage Mouse Model
作者全名："Wang, Zhenhua; Li, Yuan; Wang, Zhixu; Liao, Yuhui; Ye, Qingqing; Tang, Shilong; Wei, Ting; Xiao, Pengyu; Huang, Juan; Lu, Weitian"
作者地址："[Wang, Zhenhua; Li, Yuan; Wang, Zhixu; Liao, Yuhui; Ye, Qingqing; Tang, Shilong; Wei, Ting; Xiao, Pengyu; Huang, Juan; Lu, Weitian] Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing, Peoples R China; [Wang, Zhenhua; Li, Yuan; Wang, Zhixu; Liao, Yuhui; Ye, Qingqing; Tang, Shilong; Wei, Ting; Xiao, Pengyu; Huang, Juan; Lu, Weitian] Chongqing Med Univ, Inst Neurosci, Basic Med Coll, Chongqing, Peoples R China; [Liao, Yuhui] Sichuan Univ Arts & Sci, Dazhou, Sichuan, Peoples R China; [Tang, Shilong] Chongqing Med Univ, Dept Radiol, Childrens Hosp, Chongqing, Peoples R China"
通信作者："Huang, J; Lu, WT (通讯作者)，Chongqing Med Univ, Basic Med Coll, Dept Anat, Chongqing, Peoples R China.; Huang, J; Lu, WT (通讯作者)，Chongqing Med Univ, Inst Neurosci, Basic Med Coll, Chongqing, Peoples R China."
来源：MOLECULAR NEUROBIOLOGY
ESI学科分类：NEUROSCIENCE & BEHAVIOR
WOS号：WOS:001174104200004
JCR分区：Q1
影响因子：5.1
年份：2024
卷号：
期号：
开始页：
结束页：
文献类型：Article; Early Access
关键词：Intracerebral hemorrhage; Oxidative stress; MMP9; beta-Dystroglycan; AQP4 polarity; Edaravone
摘要："Oxidative stress (OS) is the main cause of secondary damage following intracerebral hemorrhage (ICH). The polarity expression of aquaporin-4 (AQP4) has been shown to be important in maintaining the homeostasis of water transport and preventing post-injury brain edema in various neurological disorders. This study primarily aimed to investigate the effect of the oxygen free radical scavenger, edaravone, on AQP4 polarity expression in an ICH mouse model and determine whether it involves in AQP4 polarity expression via the OS/MMP9/beta-dystroglycan (beta-DG) pathway. The ICH mouse model was established by autologous blood injection into the basal nucleus. Edaravone or the specific inhibitor of matrix metalloproteinase 9 (MMP9), MMP9-IN-1, called MMP9-inh was administered 10 min after ICH via intraperitoneal injection. ELISA detection, neurobehavioral tests, dihydroethidium staining (DHE staining), intracisternal tracer infusion, hematoxylin and eosin (HE) staining, immunofluorescence staining, western blotting, Evans blue (EB) permeability assay, and brain water content test were performed. The results showed that OS was exacerbated, AQP4 polarity was lost, drainage function of brain fluids was damaged, brain injury was aggravated, expression of AQP4, MMP9, and GFAP increased, while the expression of beta-DG decreased after ICH. Edaravone reduced OS, restored brain drainage function, reduced brain injury, and downregulated the expression of AQP4, MMP9. Both edaravone and MMP9-inh alleviated brain edema, maintained blood-brain barrier (BBB) integrity, mitigated the loss of AQP4 polarity, downregulated GFAP expression, and upregulated beta-DG expression. The current study suggests that edaravone can maintain AQP4 polarity expression by inhibiting the OS /MMP9/beta-DG pathway after ICH."
基金机构："National Natural Science Foundation of China [NSFC 82171457]; Natural Science Foundation of Chongqing [CSTB2022NSCQ-MSX1083]; Program for Youth Innovation in Future Medicine, Chongqing Medical University [W0031]"
基金资助正文："This work was supported by the National Natural Science Foundation of China (NSFC 82171457), Natural Science Foundation of Chongqing (CSTB2022NSCQ-MSX1083), and Program for Youth Innovation in Future Medicine, Chongqing Medical University (W0031)."
