Author
Listed:
- Yejie Shi
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University)
- Lili Zhang
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University
Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System)
- Hongjian Pu
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University)
- Leilei Mao
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University)
- Xiaoming Hu
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University
Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System)
- Xiaoyan Jiang
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University)
- Na Xu
(State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University)
- R. Anne Stetler
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University
Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System)
- Feng Zhang
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University
Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System)
- Xiangrong Liu
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University)
- Rehana K. Leak
(Mylan School of Pharmacy, Duquesne University)
- Richard F. Keep
(University of Michigan)
- Xunming Ji
(China-America Institute of Neuroscience, Xuanwu Hospital, Capital Medical University)
- Jun Chen
(Center of Cerebrovascular Disease Research, University of Pittsburgh School of Medicine
State Key Laboratory of Medical Neurobiology, Institute of Brain Science and the Collaborative Innovation Center for Brain Science, Fudan University
Geriatric Research, Educational and Clinical Center, Veterans Affairs Pittsburgh Health Care System)
Abstract
The mechanism and long-term consequences of early blood–brain barrier (BBB) disruption after cerebral ischaemic/reperfusion (I/R) injury are poorly understood. Here we discover that I/R induces subtle BBB leakage within 30–60 min, likely independent of gelatinase B/MMP-9 activities. The early BBB disruption is caused by the activation of ROCK/MLC signalling, persistent actin polymerization and the disassembly of junctional proteins within microvascular endothelial cells (ECs). Furthermore, the EC alterations facilitate subsequent infiltration of peripheral immune cells, including MMP-9-producing neutrophils/macrophages, resulting in late-onset, irreversible BBB damage. Inactivation of actin depolymerizing factor (ADF) causes sustained actin polymerization in ECs, whereas EC-targeted overexpression of constitutively active mutant ADF reduces actin polymerization and junctional protein disassembly, attenuates both early- and late-onset BBB impairment, and improves long-term histological and neurological outcomes. Thus, we identify a previously unexplored role for early BBB disruption in stroke outcomes, whereby BBB rupture may be a cause rather than a consequence of parenchymal cell injury.
Suggested Citation
Yejie Shi & Lili Zhang & Hongjian Pu & Leilei Mao & Xiaoming Hu & Xiaoyan Jiang & Na Xu & R. Anne Stetler & Feng Zhang & Xiangrong Liu & Rehana K. Leak & Richard F. Keep & Xunming Ji & Jun Chen, 2016.
"Rapid endothelial cytoskeletal reorganization enables early blood–brain barrier disruption and long-term ischaemic reperfusion brain injury,"
Nature Communications, Nature, vol. 7(1), pages 1-18, April.
Handle:
RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10523
DOI: 10.1038/ncomms10523
Download full text from publisher
Corrections
All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10523. See general information about how to correct material in RePEc.
If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.
We have no bibliographic references for this item. You can help adding them by using this form .
If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.
For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: Sonal Shukla or Springer Nature Abstracting and Indexing (email available below). General contact details of provider: http://www.nature.com .
Please note that corrections may take a couple of weeks to filter through
the various RePEc services.