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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2018

Open Access 01-12-2018 | Research

Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice

Authors: Zhuo Cheng, Liping Wang, Meijie Qu, Huaibin Liang, Wanlu Li, Yongfang Li, Lidong Deng, Zhijun Zhang, Guo-Yuan Yang

Published in: Journal of Neuroinflammation | Issue 1/2018

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Abstract

Background

Ischemic stroke induced matrixmetallo-proteinase-9 (MMP-9) upregulation, which increased blood-brain barrier permeability. Studies demonstrated that mesenchymal stem cell therapy protected blood-brain barrier disruption from several cerebrovascular diseases. However, the underlying mechanism was largely unknown. We therefore hypothesized that mesenchymal stem cells reduced blood-brain barrier destruction by inhibiting matrixmetallo-proteinase-9 and it was related to intercellular adhesion molecule-1 (ICAM-1).

Methods

Adult ICR male mice (n = 118) underwent 90-min middle cerebral artery occlusion and received 2 × 105 mesenchymal stem cell transplantation. Neurobehavioral outcome, infarct volume, and blood-brain barrier permeability were measured after ischemia. The relationship between myeloperoxidase (MPO) activity and ICAM-1 release was further determined.

Results

We found that intracranial injection of mesenchymal stem cells reduced infarct volume and improved behavioral function in experimental stroke models (p < 0.05). IgG leakage, tight junction protein loss, and inflammatory cytokines IL-1β, IL-6, and TNF-α reduced in mesenchymal stem cell-treated mice compared to the control group following ischemia (p < 0.05). After transplantation, MMP-9 was decreased in protein and activity levels as compared with controls (p < 0.05). Furthermore, myeloperoxidase-positive cells and myeloperoxidase activity were decreased in mesenchymal stem cell-treated mice (p < 0.05).

Conclusion

The results showed that mesenchymal stem cell therapy attenuated blood-brain barrier disruption in mice after ischemia. Mesenchymal stem cells attenuated the upward trend of MMP-9 and potentially via downregulating ICAM-1 in endothelial cells. Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) pathway may influence MMP-9 expression of neutrophils and resident cells, and ICAM-1 acted as a key factor in the paracrine actions of mesenchymal stem cell.
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Metadata
Title
Mesenchymal stem cells attenuate blood-brain barrier leakage after cerebral ischemia in mice
Authors
Zhuo Cheng
Liping Wang
Meijie Qu
Huaibin Liang
Wanlu Li
Yongfang Li
Lidong Deng
Zhijun Zhang
Guo-Yuan Yang
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2018
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-018-1153-1

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