干旱区生态环境知识资源中心(Arid): Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans

Arid

DOI	10.1371/journal.pbio.3000946
	Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans
	Mora, Pierre; Hollier, Pierre-Louis; Guimbal, Sarah; Abelanet, Alice; Diop, Aissata; Cornuault, Lauriane; Couffinhal, Thierry; Horng, Sam; Gadeau, Alain-Pierre; Renault, Marie-Ange; Chapouly, Candice
通讯作者	Chapouly, C
来源期刊	PLOS BIOLOGY
ISSN	1544-9173
EISSN	1545-7885
出版年	2020
卷号	18 期号:11
英文摘要	Inflammation of the central nervous system (CNS) induces endothelial blood-brain barrier (BBB) opening as well as the formation of a tight junction barrier between reactive astrocytes at the Glia Limitans. We hypothesized that the CNS parenchyma may acquire protection from the reactive astrocytic Glia Limitans not only during neuroinflammation but also when BBB integrity is compromised in the resting state. Previous studies found that astrocyte-derived Sonic hedgehog (SHH) stabilizes the BBB during CNS inflammatory disease, while endothelial-derived desert hedgehog (DHH) is expressed at the BBB under resting conditions. Here, we investigated the effects of endothelial Dhh on the integrity of the BBB and Glia Limitans. We first characterized DHH expression within endothelial cells at the BBB, then demonstrated that DHH is down-regulated during experimental autoimmune encephalomyelitis (EAE). Using a mouse model in which endothelial Dhh is inducibly deleted, we found that endothelial Dhh both opens the BBB via the modulation of forkhead box O1 (FoxO1) transcriptional activity and induces a tight junctional barrier at the Glia Limitans. We confirmed the relevance of this glial barrier system in human multiple sclerosis active lesions. These results provide evidence for the novel concept of chronic neuroinflammatory tolerance in which BBB opening in the resting state is sufficient to stimulate a protective barrier at the Glia Limitans that limits the severity of subsequent neuroinflammatory disease. In summary, genetic disruption of the BBB generates endothelial signals that drive the formation under resting conditions of a secondary barrier at the Glia Limitans with protective effects against subsequent CNS inflammation. The concept of a reciprocally regulated CNS double barrier system has implications for treatment strategies in both the acute and chronic phases of multiple sclerosis pathophysiology.
类型	Article
语种	英语
开放获取类型	Green Published, gold
收录类别	SCI-E
WOS记录号	WOS:000595936300002
WOS关键词	NEUROVASCULAR UNIT ; TIGHT JUNCTIONS ; UP-REGULATION ; SPINAL-CORD ; ASTROCYTES ; EXPRESSION ; HEDGEHOG ; TOLERANCE ; ISCHEMIA ; HEALTH
WOS类目	Biochemistry & Molecular Biology ; Biology
WOS研究方向	Biochemistry & Molecular Biology ; Life Sciences & Biomedicine - Other Topics
资源类型	期刊论文
条目标识符	http://119.78.100.177/qdio/handle/2XILL650/327858
作者单位	[Mora, Pierre; Hollier, Pierre-Louis; Guimbal, Sarah; Abelanet, Alice; Diop, Aissata; Cornuault, Lauriane; Couffinhal, Thierry; Gadeau, Alain-Pierre; Renault, Marie-Ange; Chapouly, Candice] Univ Bordeaux, Biol Cardiovasc Dis, INSERM, Pessac, France; [Horng, Sam] Icahn Sch Med Mt Sinai, Dept Neurol & Neurosci, New York, NY 10029 USA
推荐引用方式 GB/T 7714	Mora, Pierre,Hollier, Pierre-Louis,Guimbal, Sarah,et al. Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans[J],2020,18(11).
APA	Mora, Pierre.,Hollier, Pierre-Louis.,Guimbal, Sarah.,Abelanet, Alice.,Diop, Aissata.,...&Chapouly, Candice.(2020).Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans.PLOS BIOLOGY,18(11).
MLA	Mora, Pierre,et al."Blood-brain barrier genetic disruption leads to protective barrier formation at the Glia Limitans".PLOS BIOLOGY 18.11(2020).