The impact of endothelial cell death in the brain and its role after stroke: A systematic review

Authors:

Marietta Zille1, Maulana Ikhsan1, Yun Jiang1,2, Josephine Lampe1,2, Jan Wenzel1,2 and
Markus Schwaninger1,2
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Affiliations:

1 Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Lübeck, Germany.

2 DZHK (German Research Centre for Cardiovascular Research), partner site Hamburg/Lübeck/Kiel, Lübeck, Germany.

Keywords: 

apoptosis, autophagy, lysosome-dependent cell death, necroptosis, ischemia, vasculature.

Abbreviatons:

ASM – acid sphingomyelinase,

ATG – autophagy related,

BBB – blood brain barrier,

EC – endothelial cell,

HBMEC – human brain microvascular EC,

LDH – lactate dehydrogenase,

MTT – 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide,

OD – oxygen deprivation,

OGD – oxygen-glucose deprivation,

PI – propidium iodide,

SAH – subarachnoid hemorrhage,

TdT – terminal deoxynucleotidyl transferase,

TUNEL – TdT-mediated dUTP nick end labeling.

Corresponding Author(s):

Markus Schwaninger, Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany; Phone: +49 451 3101 7200; Fax: +49 451 3101 7204; markus.schwaninger@pharma.uni-luebeck.de Marietta Zille, Institute for Experimental and Clinical Pharmacology and Toxicology, University of Lübeck, Ratzeburger Allee 160, 23562 Lübeck, Germany; Tel.: +49 451 31017227; marietta.zille@pharma.uni-luebeck.de

Conflict of interest statement:

The authors declare no conflict of interest.

Please cite this article as:

Marietta Zille, Maulana Ikhsan, Yun Jiang, Josephine Lampe, Jan Wenzel and Markus Schwaninger (2019). The impact of endothelial cell death in the brain and its role after stroke: A systematic review. Cell Stress 3(11): 330-347. doi: 10.15698/cst2019.11.203

© 2019 Zille et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduc-tion in any medium, provided the original author and source are acknowledged.

Abstract:

The supply of oxygen and nutrients to the brain is vital for its function and requires a complex vascular network that, when disturbed, results in profound neurological dysfunction. As part of the pathology in stroke, endothelial cells die. As endothelial cell death affects the surrounding cellular environment and is a potential target for the treatment and prevention of neurological disorders, we have systematically reviewed important aspects of endothelial cell death with a particular focus on stroke. After screening 2876 publications published between January 1, 2010 and August 7, 2019, we identified 154 records to be included. We found that endothelial cell death occurs rapidly as well as later after the onset of stroke conditions. Among the different cell death mechanisms, apoptosis was the most widely investigated (92 records), followed by autophagy (20 records), while other, more recently defined mechanisms received less attention, such as lysosome-dependent cell death (2 records) and necroptosis (2 records). We also discuss the differential vulnerability of brain cells to injury after stroke and the role of endothelial cell death in the no-reflow phenomenon with a special focus on the microvasculature. Further investigation of the different cell death mechanisms using novel tools and biomarkers will greatly enhance our understanding of endothelial cell death. For this task, at least two markers/criteria are desirable to determine cell death subroutines according to the recommendations of the Nomenclature Committee on Cell Death.