Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke

doi:10.1021/acschemneuro.2c00740

科研成果详情

题名	Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke
作者	Xiong, Ye3; Fu, Yanqiong1; Li, Zhuoli1; Zheng, Yu 1; Cui, Maiyin 4; Zhang, Chan5; Huang, Xin Yi 1; Jian, Yong 2; Chen, Bai Hui 1
发表日期	2023-05-10
发表期刊	ACS CHEMICAL NEUROSCIENCE 影响因子和分区
语种	英语
原始文献类型	Article ; Early Access
关键词	laquinimod ischemic stroke microglia astrocyte BBB
其他关键词	MEMORY DEFICIT ; BRAIN ; INJURY ; NEUROGENESIS ; ASTROCYTES ; PROTECTS ; MICE ; NEUROPROTECTION ; PLASTICITY ; COGNITION
摘要	Glial activation is involved in neuroinflammation and blood-brain barrier (BBB) damage, which plays a key role in ischemic stroke-induced neuronal damage; therefore, regulating glial activation is an important way to inhibit ischemic brain injury. Effects of laquinimod (LAQ) include inhibiting axonal damage and neuroinflammation in multiple neuronal injury diseases. However, whether laquinimod can exert neuroprotective effects after ischemic stroke remains unknown. In this study, we investigated the effect of LAQ on glial activation, BBB damage, and neuronal damage in an ischemic stroke model. Adult ICR mice were used to create a photothrombotic stroke (PT) model. LAQ was administered orally at 30 min after ischemic injury. Neurobehavioral tests, Evans Blue, immunofluorescence, TUNEL, Nissl staining, and western blot were performed to evaluate the neurofunctional outcome. Quantification of immunofluorescence was evaluated by unbiased stereology. LAQ post-treatment significantly reduced infarction and improved forepaw function at 5 days after PT. Interestingly, LAQ treatment significantly promoted anti-inflammatory microglial activation. Moreover, LAQ treatment reduced astrocyte activation, glial scar formation, and BBB breakdown in ischemic brains. Therefore, this study demonstrated that LAQ post-treatment restricted microglial polarization, astrogliosis, and glial scar and improved BBB damage and behavioral function. LAQ may serve as a novel target to develop new therapeutic agents for ischemic stroke.
资助项目	National Natural Science Foundation of China[81801164];Natural Science Foundation of Zhejiang Province[LQ18H090003];Wenzhou Municipal Science & Technology Bureau Fund[Y20220047];
出版者	AMER CHEMICAL SOC
ISSN	1948-7193
卷号	14 期号:11 页码:1992-2007
DOI	10.1021/acschemneuro.2c00740
页数	16
WOS类目	Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Neurosciences
WOS研究方向	Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Neurosciences & Neurology
WOS记录号	WOS:000988460600001
收录类别	SCIE ; PUBMED ; SCOPUS
在线发表日期	2023-05
URL	查看原文
PubMed ID	3716127
SCOPUSEID	2-s2.0-85160818466
通讯作者地址	[Jian, Yong]Wenzhou Institute,University of Chinese Academy of Sciences,Zhejiang,Wenzhou,325001,China ; [Chen, Bai Hui]Department of Histology and Embryology,Institute of Neuroscience,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
Scopus学科分类	Biochemistry;Physiology;Cognitive Neuroscience;Cell Biology
引用统计
文献类型	期刊论文
条目标识符	https://kms.wmu.edu.cn/handle/3ETUA0LF/180059
专题	第一临床医学院（信息与工程学院）、附属第一医院检验医学院（生命科学学院、生物学实验教学中心）基础医学院（机能实验教学中心）_形态学系_组织胚胎学
通讯作者	Jian, Yong; Chen, Bai Hui
作者单位	1.Department of Histology and Embryology,Institute of Neuroscience,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 2.Wenzhou Institute,University of Chinese Academy of Sciences,Zhejiang,Wenzhou,325001,China; 3.The First School of Clinical Medicine,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China; 4.Department of Rehabilitation and Traditional Chinese Medicine,The Second Affiliated Hospital of Zhejiang University School of Medicine,Zhejiang,Hangzhou,310052,China; 5.School of Laboratory Medicine and Life Sciences,Wenzhou Medical University,Zhejiang,Wenzhou,325035,China
第一作者单位	温州医科大学
通讯作者单位	组织胚胎学
第一作者的第一单位	温州医科大学
推荐引用方式 GB/T 7714	Xiong, Ye,Fu, Yanqiong,Li, Zhuoli,et al. Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke[J]. ACS CHEMICAL NEUROSCIENCE,2023,14(11):1992-2007.
APA	Xiong, Ye., Fu, Yanqiong., Li, Zhuoli., Zheng, Yu., Cui, Maiyin., ... & Chen, Bai Hui. (2023). Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke. ACS CHEMICAL NEUROSCIENCE, 14(11), 1992-2007.
MLA	Xiong, Ye,et al."Laquinimod Inhibits Microglial Activation, Astrogliosis, BBB Damage, and Infarction and Improves Neurological Damage after Ischemic Stroke".ACS CHEMICAL NEUROSCIENCE 14.11(2023):1992-2007.