Authors:	Neulen, Axel Pantel, Tobias Kosterhon, Michael Kramer, Andreas Kunath, Sascha Petermeyer, Maximilian Moosmann, Bernd Lotz, Johannes Kantelhardt, Sven Rainer Ringel, Florian Thal, Serge
Title:	Neutrophils mediate early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage
Online publication date:	8-Nov-2019
Year of first publication:	2019
Language:	english
Abstract:	Cerebral hypoperfusion in the first hours after subarachnoid haemorrhage (SAH) is a major determinant of poor neurological outcome. However, the underlying pathophysiology is only partly understood. Here we induced neutropenia in C57BL/6N mice by anti-Ly6G antibody injection, induced SAH by endovascular filament perforation, and analysed cerebral cortical perfusion with laser SPECKLE contrast imaging to investigate the role of neutrophils in mediating cerebral hypoperfusion during the first 24 h post-SAH. SAH induction significantly increased the intracranial pressure (ICP), and significantly reduced the cerebral perfusion pressure (CPP). At 3 h after SAH, ICP had returned to baseline and CPP was similar between SAH and sham mice. However, in SAH mice with normal neutrophil counts cortical hypoperfusion persisted. Conversely, despite similar CPP, cortical perfusion was significantly higher at 3 h after SAH in mice with neutropenia. The levels of 8-iso-prostaglandin-F2α in the subarachnoid haematoma increased significantly at 3 h after SAH in animals with normal neutrophil counts indicating oxidative stress, which was not the case in neutropenic SAH animals. These results suggest that neutrophils are important mediators of cortical hypoperfusion and oxidative stress early after SAH. Targeting neutrophil function and neutrophil-induced oxidative stress could be a promising new approach to mitigate cerebral hypoperfusion early after SAH.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-221
Version:	Published version
Publication type:	Zeitschriftenaufsatz
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Scientific reports 9
Pages or article number:	Art. 8460
Publisher:	Macmillan Publishers Limited, part of Springer Nature
Publisher place:	London
Issue date:	2019
ISSN:	2045-2322
Publisher URL:	http://dx.doi.org/10.1038/s41598-019-44906-9
Publisher DOI:	10.1038/s41598-019-44906-9
Appears in collections:	JGU-Publikationen