Protective role of reactive astrocytes in brain ischemia

被引：438

作者：

Li, Lizhen ^{[1
]}

Lundkvist, Andrea ^{[1
]}

Andersson, Daniel ^{[1
]}

Wilhelmsson, Ulrika ^{[1
]}

Nagai, Nobuo ^{[2
]}

Pardo, Andrea C. ^{[3
]}

Nodin, Christina ^{[1
]}

Stahlberg, Anders ^{[4
,5
]}

Aprico, Karina ^{[1
]}

Larsson, Kerstin ^{[6
]}

Yabe, Takeshi ^{[7
]}

Moons, Lieve ^{[2
]}

Fotheringham, Andrew ^{[8
,9
]}

Davies, Ioan ^{[8
,9
]}

Carmeliet, Peter ^{[2
]}

Schwartz, Joan P. ^{[7
]}

Pekna, Marcela ^{[6
]}

Kubista, Mikael ^{[4
,5
]}

Blomstrand, Fredrik ^{[1
]}

Maragakis, Nicholas ^{[3
]}

Nilsson, Michael ^{[1
]}

Pekny, Milos ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Clin Neurosci & Rehabil,Ctr Brain Repair & R, SE-40530 Gothenburg, Sweden

[2] KU Leuven VIB, Ctr Transgene Technol & Gene Therapy, Louvain, Belgium

[3] Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD USA

[4] Chalmers, Dept Chem & Biosci, S-41296 Gothenburg, Sweden

[5] TATAA Bioctr, Gothenburg, Sweden

[6] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Med Chem & Cell Biol, SE-40530 Gothenburg, Sweden

[7] Natl Inst Neurol Disorders & Stroke, Neurotroph Factors Sect, NIH, Bethesda, MD USA

[8] Univ Manchester, Sch Med, Manchester, Lancs, England

[9] Univ Manchester, Sch Biol Sci, Manchester, Lancs, England

来源：

JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM | 2008年 / 28卷 / 03期

关键词：

astrocytes; GFAP; intermediate filaments; reactive gliosis (astrogliosis); vimentin;

D O I：

10.1038/sj.jcbfm.9600546

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Reactive astrocytes are thought to protect the penumbra during brain ischemia, but direct evidence has been lacking due to the absence of suitable experimental models. Previously, we generated mice deficient in two intermediate filament ( IF) proteins, glial fibrillary acidic protein (GFAP) and vimentin, whose upregulation is the hallmark of reactive astrocytes. GFAP(-/-) Vim(-/-) mice exhibit attenuated posttraumatic reactive gliosis, improved integration of neural grafts, and posttraumatic regeneration. Seven days after middle cerebral artery ( MCA) transection, infarct volume was 210 to 350% higher in GFAP(-/-) Vim(-/-) than in wild-type (WT) mice; GFAP(-/-), Vim(-/-) and WT mice had the same infarct volume. Endothelin B receptor (ETBR) immunoreactivity was strong on cultured astrocytes and reactive astrocytes around infarct in WT mice but undetectable in GFAP(-/-) Vim(-/-) astrocytes. In WT astrocytes, ETBR colocalized extensively with bundles of IFs. GFAP(-/-) Vim(-/-) astrocytes showed attenuated endothelin-3-induced blockage of gap junctions. Total and glutamate transporter-1 (GLT-1)-mediated glutamate transport was lower in GFAP(-/-) Vim(-/-) than in WT mice. DNA array analysis and quantitative real-time PCR showed down-regulation of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of tissue plasminogen activator. Thus, reactive astrocytes have a protective role in brain ischemia, and the absence of astrocyte IFs is linked to changes in glutamate transport, ETBR-mediated control of gap junctions, and PAI-1 expression.

引用

页码：468 / 481

页数：14

共 45 条

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