p Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4

doi:10.7150/ijbs.64187

科研成果详情

题名	p Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4
作者	Lu, Qi 1; Xiong, Jun 1; Yuan, Yuan1,2; Ruan, Zhanwei3; Zhang, Yu1; Chai, Bo 1; Li, Lei1; Cai, Shufang 4; Xiao, Jian1; Wu, Yanqing 4; Huang, Peng5; Zhang, Hongyu1,6
发表日期	2022
发表期刊	INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 影响因子和分区
语种	英语
原始文献类型	Article
关键词	Traumatic brain injury (TBI) Minocycline Aquaporin-4 (AQP4) Blood-brain barrier (BBB) Astrocytes
其他关键词	BARRIER DAMAGE ; MOUSE MODEL ; EDEMA ; DISRUPTION ; AQP4 ; ASTROCYTES ; MECHANISMS ; PROTECTS ; TARGET
摘要	Traumatic brain injury (TBI) is one of the main concerns worldwide as there is still no comprehensive therapeutic intervention. Astrocytic water channel aquaporin-4 (AQP-4) system is closely related to the brain edema, water transport at blood-brain barrier (BBB) and astrocyte function in the central nervous system (CNS). Minocycline, a broad-spectrum semisynthetic tetracycline antibiotic, has shown anti-inflammation, anti-apoptotic, vascular protection and neuroprotective effects on TBI models. Here, we tried to further explore the underlying mechanism of minocycline treatment for TBI, especially the relationship of minocycline and AQP4 during TBI treatment. In present study, we observed that minocycline efficaciously reduces the elevation of AQP4 in TBI mice. Furthermore, minocycline significantly reduced neuronal apoptosis, ameliorated brain edema and BBB disruption after TBI. In addition, the expressions of tight junction protein and astrocyte morphology alteration were optimized by minocycline administration. Similar results were found after treating with TGN-020 (an inhibitor of AQP4) in TBI mice. Moreover, these effects were reversed by cyanamide (CYA) treatment, which notably upregulated AQP4 expression level in vivo. In primary cultured astrocytes, small-interfering RNA (siRNA) AQP4 treatment prevented glutamate-induced astrocyte swelling. To sum up, our study suggests that minocycline improves the functional recovery of TBI through reducing AQP4 level to optimize BBB integrity and astrocyte function, and highlights that the AQP4 may be an important therapeutic target during minocycline treating for TBI.
资助项目	National Natural Science Foundation of ChinaNational Natural Science Foundation of China (NSFC) [81772450, 81972150, 81801233]; Zhejiang Provincial Natural Science FoundationNatural Science Foundation of Zhejiang Province [LQ18H150003, LQ20C200015]; CAMS Innovation Fund for Medical Sciences [2019-I2M-5-028]
出版者	IVYSPRING INT PUBL
出版地	LAKE HAVEN
ISSN	1449-2288
卷号	18 期号:1 页码:441-458
DOI	10.7150/ijbs.64187
页数	18
WOS类目	Biochemistry & Molecular Biology ; Biology
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
WOS记录号	WOS:000741493200005
收录类别	SCIE ; PUBMED ; SCOPUS
URL	查看原文
PubMed ID	34975343
PMC记录号	PMC8692149
SCOPUSEID	2-s2.0-85123036602
通讯作者地址	[Wu, Yanqing]The Institute of Life Sciences,Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors,Biomedical Collaborative Innovation Center of Wenzhou,Wenzhou University,Zhejiang,Wenzhou,325035,China ; [Huang, Peng]Department of Pharmacy,Ruian People’s Hospital,The Third Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325200,China ; [Zhang, Hongyu]School of Pharmaceutical Sciences,Wenzhou Wound Repair and Regeneration Key Laboratory,Cixi Biomedical Research Institute,Wenzhou Medical University,Zhejiang,Wenzhou,325000,China
Scopus学科分类	Ecology, Evolution, Behavior and Systematics;Applied Microbiology and Biotechnology;Molecular Biology;Developmental Biology;Cell Biology
引用统计	被引频次：2[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/6967
专题	药学院（分析测试中心）研究生工作部（研究生院）其他_附属第三医院（瑞安市人民医院）其他_附属诸暨医院（诸暨市人民医院）
通讯作者	Wu, Yanqing; Huang, Peng; Zhang, Hongyu
作者单位	1.School of Pharmaceutical Sciences,Wenzhou Wound Repair and Regeneration Key Laboratory,Cixi Biomedical Research Institute,Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 2.Department of pharmacy,Hangzhou Red Cross Hospital,Zhejiang Province Hospital of Integrated Traditional Chinese and Western Medicine,Zhejiang,Hangzhou,310003,China; 3.Department of Emergency,Ruian People’s Hospital,The Third Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325000,China; 4.The Institute of Life Sciences,Engineering Laboratory of Zhejiang Province for Pharmaceutical Development of Growth Factors,Biomedical Collaborative Innovation Center of Wenzhou,Wenzhou University,Zhejiang,Wenzhou,325035,China; 5.Department of Pharmacy,Ruian People’s Hospital,The Third Affiliated Hospital of Wenzhou Medical University,Zhejiang,Wenzhou,325200,China; 6.Department of Pharmacy,Zhuji People’s Hospital,The Affiliated Hospital of Wenzhou Medical University,Zhejiang,Shaoxing,311899,China
第一作者单位	药学院（分析测试中心）
通讯作者单位	附属第三医院（瑞安市人民医院）; 药学院（分析测试中心）
第一作者的第一单位	药学院（分析测试中心）
推荐引用方式 GB/T 7714	Lu, Qi,Xiong, Jun,Yuan, Yuan,et al. p Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,2022,18(1):441-458.
APA	Lu, Qi., Xiong, Jun., Yuan, Yuan., Ruan, Zhanwei., Zhang, Yu., ... & Zhang, Hongyu. (2022). p Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4. INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES, 18(1), 441-458.
MLA	Lu, Qi,et al."p Minocycline improves the functional recovery after traumatic brain injury via inhibition of aquaporin-4".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 18.1(2022):441-458.