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70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

12.05. - 15.05.2019, Würzburg

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Neutrophils induce early cerebral cortical hypoperfusion in a murine model of subarachnoid haemorrhage

Neutrophile Granulozyten induzieren eine frühe zerebrale kortikale Hypoperfusion in einem Mausmodell der Subarachnoidalblutung

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  • presenting/speaker Axel Neulen - Universitätsmedizin Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Tobias Pantel - Universitätsmedizin Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Michael Kosterhon - Universitätsmedizin Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Andreas Kramer - Universitätsmedizin Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Sascha Kunath - Universitätsmedizin Mainz, Institut für Pathobiochemie, Mainz, Deutschland
  • Bernd Moosmann - Universitätsmedizin Mainz, Institut für Pathobiochemie, Mainz, Deutschland
  • Johannes Lotz - Universitätsmedizin Mainz, Institut für Klinische Chemie und Laboratoriumsmedizin, Mainz, Deutschland
  • Sven Rainer Kantelhardt - Universitätsmedizin Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Florian Ringel - Universitätsmedizin Mainz, Neurochirurgische Klinik und Poliklinik, Mainz, Deutschland
  • Serge C. Thal - Universitätsmedizin Mainz, Klinik für Anästhesiologie, Mainz, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 70. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Skandinavischen Gesellschaft für Neurochirurgie. Würzburg, 12.-15.05.2019. Düsseldorf: German Medical Science GMS Publishing House; 2019. DocP013

doi: 10.3205/19dgnc351, urn:nbn:de:0183-19dgnc3512

Published: May 8, 2019

© 2019 Neulen et al.
This is an Open Access article distributed under the terms of the Creative Commons Attribution 4.0 License. See license information at http://creativecommons.org/licenses/by/4.0/.

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Objective: Accumulated evidence suggests that cerebral hypoperfusion during the first hours after subarachnoid hemorrhage (SAH) is critical for neurological outcome. However, the mechanisms leading to cerebral hypoperfusion during this phase are still unclear. As animal studies have shown that a depletion of neutrophils improves neurological outcome after SAH, we set out to investigate the role of neutrophils in mediating cerebral cortical hypoperfusion during the first 24h after SAH.

Methods: SAH was induced in C57BL/6N mice by endovascular filament perforation. Neutropenia was induced by anti-Ly6G antibody injection 12h prior to surgery. Cerebral cortical perfusion was determined before, and 15min, 3h, and 24h after SAH using laser SPECKLE contrast imaging, and expressed as % baseline. As surrogate parameter for oxidative stress, 8-isoprostane levels were determined in the subarachnoid hematoma. The Mann-Whitney U test was used for statistical testing with p<0.05 considered as statistically significant.

Results: Induction of SAH significantly increased intracranial pressure (ICP) (SAH: 84.5±10.1 mmHg, sham: 16.6±1.4, p<0.001), which was associated with a significant reduction of cerebral perfusion pressure (CPP) (SAH: -1.2±10.2 mmHg, sham: 74.1±6.1 mmHg, p<0.001) immediately after SAH. At 3h after SAH ICP had returned to baseline and CPP between SAH and sham was similar. When SAH animals with normal neutrophil counts were compared to SAH animals with neutropenia, cerebral cortical perfusion was significantly better at 3h after SAH (SAH, neutropenia: 99±11% vs. SAH, control: 65±8%, p<0.05), whereas CPP was similar (SAH, neutropenia: 64.4±4.8 mmHg vs. SAH, control: 60.0±4.2 mmHg, n.s.). Levels of 8-isoprostane in the subarachnoid hematoma increased significantly at 3h after SAH in animals with normal neutrophil counts, which was not the case in SAH animals with neutropenia (neutropenia: 395.0±83.5 ng 8-isoprostane/g protein; control: 668.0±122.5 ng/g).

Conclusion: Already in the first hours after SAH, neutrophils are important mediators of cortical hypoperfusion and oxidative stress. Targeting neutrophil function or neutrophil interaction with the neurovascular unit could therefore be a promising strategy to improve cerebral hypoperfusion in the early phase after SAH.