Translational Stroke Research

, Volume 10, Issue 5, pp 566–582 | Cite as

The Acute Phase of Experimental Subarachnoid Hemorrhage: Intracranial Pressure Dynamics and Their Effect on Cerebral Blood Flow and Autoregulation

  • Catharina Conzen
  • Katrin Becker
  • Walid Albanna
  • Miriam Weiss
  • Annika Bach
  • Nyanda Lushina
  • André Steimers
  • Sarah Pinkernell
  • Hans Clusmann
  • Ute Lindauer
  • Gerrit A. SchubertEmail author
Original Article


Clinical presentation and neurological outcome in subarachnoid hemorrhage (SAH) is highly variable. Aneurysmal SAH (aSAH) is hallmarked by sudden increase of intracranial pressure (ICP) and acute hypoperfusion contributing to early brain injury (EBI) and worse outcome, while milder or non-aneurysmal SAH with comparable amount of blood are associated with better neurological outcome, possibly due to less dramatic changes in ICP. Acute pressure dynamics may therefore be an important pathophysiological aspect determining neurological complications and outcome. We investigated the influence of ICP variability on acute changes after SAH by modulating injection velocity and composition in an experimental model of SAH. Five hundred microliters of arterial blood (AB) or normal saline (NS) were injected intracisternally over 1 (AB1, NS1), 10 (AB10, NS10), or 30 min (AB30) with monitoring for 6 h (n = 68). Rapid blood injection resulted in highest ICP peaks (AB1 median 142.7 mmHg [1.Q 116.7–3.Q 230.6], AB30 33.42 mmHg [18.8–38.3], p < 0.001) and most severe hypoperfusion (AB1 16.6% [11.3–30.6], AB30 44.2% [34.8–59.8]; p < 0.05). However, after 30 min, all blood groups showed comparable ICP elevation and prolonged hypoperfusion. Cerebral autoregulation was disrupted initially due to the immediate ICP increase in all groups except NS10; only AB1, however, resulted in sustained impairment of autoregulation, as well as early neuronal cell loss. Rapidity and composition of hemorrhage resulted in characteristic hyperacute hemodynamic changes, with comparable hypoperfusion despite different ICP ranges. Only rapid ICP increase was associated with pronounced and early, but sustained disruption of cerebral autoregulation, possibly contributing to EBI.


Experimental subarachnoid hemorrhage Acute phase Cerebral autoregulation Early brain injury (EBI) Intracranial pressure (ICP) Cerebral hypoperfusion 



We cordially thank Ekaterina Harder, Jörn Iwertowski (Translational Neurosurgery and Neurobiology) and Birgit Nellessen (Dept. of Anesthesiology, RWTH Aachen University) for technical assistance. Further technical support was provided by the Immunohistochemistry Facility, a core facility of the Interdisciplinary Center for Clinical Research (IZKF) Aachen within the Faculty of Medicine at RWTH Aachen University.

Author Contribution

Conceived and designed the experiments and the study protocol: CC, GAS, UL. Performed the experiments: CC, KB. Analyzed the data: CC, UL, GAS, WA. Interpretation of the data: CC, GAS, UL. Designed and performed immunohistochemistry: CC, AB, KB. Blinded cell counting: NL. Blinded analysis of successful SAH: MW. Contributed reagents/materials/analysis tools: AS, WA, CC, UL, HC, GAS, SP, MW, KB. Wrote the paper: CC, KB, GAS. Critical review of the manuscript: UL, HC, MW, AS, WA, AB, KB.


This study was supported by grants from DFG (FOR 2591) and by grants from the Foundation of Neurosurgical Research (German Society of Neurosurgery, 2016).

Compliance with Ethical Standards

Ethical Approval

All applicable international, national, and institutional guidelines for the care and use of animals were followed. All experimental protocols were approved by the responsible state authorities in line with the EU Directive 2010/63/EU on the protection of animals used for scientific purposes (Landesamt für Natur, Umwelt und Verbraucherschutz (LANUV) Nordrhein – Westfalen, Recklinghausen, Germany; AZ 84-02.04.2015.A412) and were performed in accordance with the ARRIVE Guidelines [21].

Conflict Interests

The authors declare that there is no conflict of interest.

Supplementary material

12975_2018_674_MOESM1_ESM.docx (3.2 mb)
ESM 1 (DOCX 3254 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Catharina Conzen
    • 1
    • 2
  • Katrin Becker
    • 2
  • Walid Albanna
    • 1
  • Miriam Weiss
    • 1
  • Annika Bach
    • 2
  • Nyanda Lushina
    • 2
  • André Steimers
    • 3
  • Sarah Pinkernell
    • 2
  • Hans Clusmann
    • 1
  • Ute Lindauer
    • 1
    • 2
  • Gerrit A. Schubert
    • 1
    Email author
  1. 1.Department of NeurosurgeryRWTH Aachen UniversityAachenGermany
  2. 2.Translational Neurosurgery and NeurobiologyRWTH Aachen UniversityAachenGermany
  3. 3.Institute for Occupational Safety and Health of the German Social Accident InsuranceSankt AugustinGermany

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