Advertisement

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

Abstract

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.

Keywords

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

Notes

Acknowledgments

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.

Funding

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)

References

  1. 1.
    Macdonald RL, Schweizer TA. Spontaneous subarachnoid haemorrhage. Lancet. 2017;389(10069):655–66.CrossRefGoogle Scholar
  2. 2.
    Vergouwen MD, Vermeulen M, van Gijn J, Rinkel GJ, Wijdicks EF, Muizelaar JP, et al. Definition of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage as an outcome event in clinical trials and observational studies: proposal of a multidisciplinary research group. Stroke. 2010;41(10):2391–5.CrossRefGoogle Scholar
  3. 3.
    Schubert GA, Seiz M, Hegewald AA, Manville J, Thome C. Acute hypoperfusion immediately after subarachnoid hemorrhage: a xenon contrast-enhanced CT study. J Neurotrauma. 2009;26(12):2225–31.CrossRefGoogle Scholar
  4. 4.
    Schubert GA, Seiz M, Hegewald AA, Manville J, Thome C. Hypoperfusion in the acute phase of subarachnoid hemorrhage. Acta Neurochir Suppl. 2011;110(Pt 1):35–8.Google Scholar
  5. 5.
    Westermaier T, Jauss A, Eriskat J, Kunze E, Roosen K. Acute vasoconstriction: decrease and recovery of cerebral blood flow after various intensities of experimental subarachnoid hemorrhage in rats. J Neurosurg. 2009;110(5):996–1002.CrossRefGoogle Scholar
  6. 6.
    Westermaier T, Jauss A, Eriskat J, Kunze E, Roosen K. Time-course of cerebral perfusion and tissue oxygenation in the first 6 h after experimental subarachnoid hemorrhage in rats. J Cereb Blood Flow Metab. 2009;29(4):771–9.CrossRefGoogle Scholar
  7. 7.
    Bederson JB, Levy AL, Ding WH, Kahn R, DiPerna CA, Jenkins AL 3rd, et al. Acute vasoconstriction after subarachnoid hemorrhage. Neurosurgery. 1998;42(2):352–60 discussion 60-2.CrossRefGoogle Scholar
  8. 8.
    Chen S, Feng H, Sherchan P, Klebe D, Zhao G, Sun X, et al. Controversies and evolving new mechanisms in subarachnoid hemorrhage. Prog Neurobiol. 2014;115:64–91.CrossRefGoogle Scholar
  9. 9.
    Sehba FA, Hou J, Pluta RM, Zhang JH. The importance of early brain injury after subarachnoid hemorrhage. Prog Neurobiol. 2012 Apr;97(1):14–37.CrossRefGoogle Scholar
  10. 10.
    Foreman B. The pathophysiology of delayed cerebral ischemia. J Clin Neurophysiol. 2016;33(3):174–82.CrossRefGoogle Scholar
  11. 11.
    Rouchaud A, Lehman VT, Murad MH, Burrows A, Cloft HJ, Lindell EP, et al. Nonaneurysmal perimesencephalic hemorrhage is associated with deep cerebral venous drainage anomalies: a systematic literature review and meta-analysis. AJNR Am J Neuroradiol. 2016;37(9):1657–63.CrossRefGoogle Scholar
  12. 12.
    Suwatcharangkoon S, Meyers E, Falo C, Schmidt JM, Agarwal S, Claassen J, et al. Loss of consciousness at onset of subarachnoid hemorrhage as an important marker of early brain injury. JAMA Neurol. 2016;73(1):28–35.CrossRefGoogle Scholar
  13. 13.
    Marbacher S, Neuschmelting V, Andereggen L, Widmer HR, von Gunten M, Takala J, et al. Early brain injury linearly correlates with reduction in cerebral perfusion pressure during the hyperacute phase of subarachnoid hemorrhage. Intensive Care Med Exp. 2014;2(1):30.CrossRefGoogle Scholar
  14. 14.
    Prunell GF, Svendgaard NA, Alkass K, Mathiesen T. Delayed cell death related to acute cerebral blood flow changes following subarachnoid hemorrhage in the rat brain. J Neurosurg. 2005;102(6):1046–54.CrossRefGoogle Scholar
  15. 15.
    Santos GA, Petersen N, Zamani AA, Du R, LaRose S, Monk A, et al. Pathophysiologic differences in cerebral autoregulation after subarachnoid hemorrhage. Neurology. 2016;86(21):1950–6.CrossRefGoogle Scholar
  16. 16.
    Budohoski KP, Czosnyka M, Smielewski P, Kasprowicz M, Helmy A, Bulters D, et al. Impairment of cerebral autoregulation predicts delayed cerebral ischemia after subarachnoid hemorrhage: a prospective observational study. Stroke. 2012;43(12):3230–7.CrossRefGoogle Scholar
  17. 17.
    Jaeger M, Soehle M, Schuhmann MU, Meixensberger J. Clinical significance of impaired cerebrovascular autoregulation after severe aneurysmal subarachnoid hemorrhage. Stroke. 2012;43(8):2097–101.CrossRefGoogle Scholar
  18. 18.
    Budohoski KP, Czosnyka M, Kirkpatrick PJ, Smielewski P, Steiner LA, Pickard JD. Clinical relevance of cerebral autoregulation following subarachnoid haemorrhage. Nat Rev Neurol. 2013;9(3):152–63.CrossRefGoogle Scholar
  19. 19.
    Schmieder K, Moller F, Engelhardt M, Scholz M, Schregel W, Christmann A, et al. Dynamic cerebral autoregulation in patients with ruptured and unruptured aneurysms after induction of general anesthesia. Zentralblatt fur Neurochirurgie. 2006;67(2):81–7.CrossRefGoogle Scholar
  20. 20.
    Jaeger M, Schuhmann MU, Soehle M, Nagel C, Meixensberger J. Continuous monitoring of cerebrovascular autoregulation after subarachnoid hemorrhage by brain tissue oxygen pressure reactivity and its relation to delayed cerebral infarction. Stroke. 2007;38(3):981–6.CrossRefGoogle Scholar
  21. 21.
    Kilkenny C, Browne WJ, Cuthill IC, Emerson M, Altman DG. Improving bioscience research reporting: the ARRIVE guidelines for reporting animal research. PLoS Biol. 2010;8(6):e1000412.CrossRefGoogle Scholar
  22. 22.
    Schubert GA, Poli S, Mendelowitsch A, Schilling L, Thome C. Hypothermia reduces early hypoperfusion and metabolic alterations during the acute phase of massive subarachnoid hemorrhage: a laser-Doppler-flowmetry and microdialysis study in rats. J Neurotrauma. 2008;25(5):539–48.CrossRefGoogle Scholar
  23. 23.
    Steimers A, Gramer M, Takagaki M, Graf R, Lindauer U, Kohl-Bareis M. Simultaneous imaging of cortical blood flow and haemoglobin concentration with LASCA and RGB reflectometry. Adv Exp Med Biol. 2013;789:427–33.CrossRefGoogle Scholar
  24. 24.
    Sugawara T, Ayer R, Jadhav V, Zhang JH. A new grading system evaluating bleeding scale in filament perforation subarachnoid hemorrhage rat model. J Neurosci Methods. 2008;167(2):327–34.CrossRefGoogle Scholar
  25. 25.
    Schneider CA, Rasband WS, Eliceiri KW. NIH Image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9(7):671–5.CrossRefGoogle Scholar
  26. 26.
    Czosnyka M, Smielewski P, Kirkpatrick P, Laing RJ, Menon D, Pickard JD. Continuous assessment of the cerebral vasomotor reactivity in head injury. Neurosurgery. 1997;41(1):11–7 discussion 7-9.CrossRefGoogle Scholar
  27. 27.
    Donnelly J, Budohoski KP, Smielewski P, Czosnyka M. Regulation of the cerebral circulation: bedside assessment and clinical implications. Crit Care. 2016;20(1):129.CrossRefGoogle Scholar
  28. 28.
    Sanchez-Porras R, Santos E, Czosnyka M, Zheng Z, Unterberg AW, Sakowitz OW. ‘Long’ pressure reactivity index (L-PRx) as a measure of autoregulation correlates with outcome in traumatic brain injury patients. Acta Neurochir. 2012;154(9):1575–81.CrossRefGoogle Scholar
  29. 29.
    Salary M, Quigley MR, Wilberger JE Jr. Relation among aneurysm size, amount of subarachnoid blood, and clinical outcome. J Neurosurg. 2007;107(1):13–7.CrossRefGoogle Scholar
  30. 30.
    Konczalla J, Schmitz J, Kashefiolasl S, Senft C, Seifert V, Platz J. Non-aneurysmal subarachnoid hemorrhage in 173 patients: a prospective study of long-term outcome. Eur J Neurol. 2015;22(10):1329–36.CrossRefGoogle Scholar
  31. 31.
    Raya A, Zipfel GJ, Diringer MN, Dacey RG Jr, Derdeyn CP, Rich KM, et al. Pattern not volume of bleeding predicts angiographic vasospasm in nonaneurysmal subarachnoid hemorrhage. Stroke. 2014;45(1):265–7.CrossRefGoogle Scholar
  32. 32.
    Kapadia A, Schweizer TA, Spears J, Cusimano M, Macdonald RL. Nonaneurysmal perimesencephalic subarachnoid hemorrhage: diagnosis, pathophysiology, clinical characteristics, and long-term outcome. World Neurosurg. 2014;82(6):1131–43.CrossRefGoogle Scholar
  33. 33.
    Dickinson CJ. Reappraisal of the Cushing reflex: the most powerful neural blood pressure stabilizing system. Clin Sci. 1990;79(6):543–50.CrossRefGoogle Scholar
  34. 34.
    Sorrentino E, Diedler J, Kasprowicz M, Budohoski KP, Haubrich C, Smielewski P, et al. Critical thresholds for cerebrovascular reactivity after traumatic brain injury. Neurocrit Care. 2012;16(2):258–66.CrossRefGoogle Scholar
  35. 35.
    Bijlenga P, Czosnyka M, Budohoski KP, Soehle M, Pickard JD, Kirkpatrick PJ, et al. “Optimal cerebral perfusion pressure” in poor grade patients after subarachnoid hemorrhage. Neurocrit Care. 2010;13(1):17–23.CrossRefGoogle Scholar
  36. 36.
    Ebel H, Rust DS, Leschinger A, Ehresmann N, Kranz A, Hoffmann O, et al. Vasomotion, regional cerebral blood flow and intracranial pressure after induced subarachnoid haemorrhage in rats. Zentralblatt fur Neurochirurgie. 1996;57(3):150–5.Google Scholar
  37. 37.
    Steiner L, Lofgren J, Zwetnow NN. Lethal mechanism in repeated subarachnoid hemorrhage in dogs. Acta Neurol Scand. 1975;52(4):268–93.CrossRefGoogle Scholar
  38. 38.
    Lee JY, Sagher O, Keep R, Hua Y, Xi G. Comparison of experimental rat models of early brain injury after subarachnoid hemorrhage. Neurosurgery. 2009;65(2):331–43 discussion 43.CrossRefGoogle Scholar
  39. 39.
    Fragata I, Canto-Moreira N, Canhao P. Comparison of cerebral perfusion in perimesencephalic subarachnoid hemorrhage and aneurysmal subarachnoid hemorrhage. Neuroradiology. 2018;60(6):609–16.CrossRefGoogle Scholar
  40. 40.
    Bederson JB, Germano IM, Guarino L. Cortical blood flow and cerebral perfusion pressure in a new noncraniotomy model of subarachnoid hemorrhage in the rat. Stroke. 1995;26(6):1086–91 discussion 91-2.CrossRefGoogle Scholar
  41. 41.
    Ansar S, Edvinsson L. Equal contribution of increased intracranial pressure and subarachnoid blood to cerebral blood flow reduction and receptor upregulation after subarachnoid hemorrhage. Laboratory investigation. J Neurosurg. 2009 Nov;111(5):978–87.CrossRefGoogle Scholar
  42. 42.
    Boedtkjer E. Acid-base regulation and sensing: accelerators and brakes in metabolic regulation of cerebrovascular tone. J Cereb Blood Flow Metab. 2017:271678X17733868.Google Scholar
  43. 43.
    Schain AJ, Melo-Carrillo A, Strassman AM, Burstein R. Cortical spreading depression closes paravascular space and impairs glymphatic flow: implications for migraine headache. J Neurosci. 2017;37(11):2904–15.CrossRefGoogle Scholar
  44. 44.
    Balbi M, Koide M, Schwarzmaier SM, Wellman GC, Plesnila N. Acute changes in neurovascular reactivity after subarachnoid hemorrhage in vivo. J Cereb Blood Flow Metab. 2015;16.Google Scholar
  45. 45.
    Balbi M, Koide M, Wellman GC, Plesnila N. Inversion of neurovascular coupling after subarachnoid hemorrhage in vivo. J Cereb Blood Flow Metab. 2017:271678X16686595.Google Scholar
  46. 46.
    Springborg JB, Ma X, Rochat P, Knudsen GM, Amtorp O, Paulson OB, et al. A single subcutaneous bolus of erythropoietin normalizes cerebral blood flow autoregulation after subarachnoid haemorrhage in rats. Br J Pharmacol. 2002;135(3):823–9.CrossRefGoogle Scholar
  47. 47.
    Yamamoto S, Nishizawa S, Tsukada H, Kakiuchi T, Yokoyama T, Ryu H, et al. Cerebral blood flow autoregulation following subarachnoid hemorrhage in rats: chronic vasospasm shifts the upper and lower limits of the autoregulatory range toward higher blood pressures. Brain Res. 1998;782(1–2):194–201.CrossRefGoogle Scholar
  48. 48.
    Friedrich V, Flores R, Sehba FA. Cell death starts early after subarachnoid hemorrhage. Neurosci Lett. 2012;512(1):6–11.CrossRefGoogle Scholar
  49. 49.
    Hollig A, Weinandy A, Nolte K, Clusmann H, Rossaint R, Coburn M. Experimental subarachnoid hemorrhage in rats: comparison of two endovascular perforation techniques with respect to success rate, confounding pathologies and early hippocampal tissue lesion pattern. PLoS One. 2015;10(4):e0123398.CrossRefGoogle Scholar
  50. 50.
    Schneider UC, Davids AM, Brandenburg S, Muller A, Elke A, Magrini S, et al. Microglia inflict delayed brain injury after subarachnoid hemorrhage. Acta Neuropathol. 2015;130(2):215–31.CrossRefGoogle Scholar
  51. 51.
    Hop JW, Rinkel GJ, Algra A, van Gijn J. Initial loss of consciousness and risk of delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage. Stroke. 1999;30(11):2268–71.CrossRefGoogle Scholar
  52. 52.
    Konczalla J, Platz J, Schuss P, Vatter H, Seifert V, Guresir E. Non-aneurysmal non-traumatic subarachnoid hemorrhage: patient characteristics, clinical outcome and prognostic factors based on a single-center experience in 125 patients. BMC Neurol. 2014;14:140.CrossRefGoogle Scholar
  53. 53.
    Shimoda M, Hoshikawa K, Shiramizu H, Oda S, Yoshiyama M, Osada T, et al. Early infarction detected by diffusion-weighted imaging in patients with subarachnoid hemorrhage. Acta Neurochir. 2010;152(7):1197–205.CrossRefGoogle Scholar
  54. 54.
    Prunell GF, Mathiesen T, Diemer NH, Svendgaard NA. Experimental subarachnoid hemorrhage: subarachnoid blood volume, mortality rate, neuronal death, cerebral blood flow, and perfusion pressure in three different rat models. Neurosurgery. 2003;52(1):165–75 discussion 75-6.Google Scholar

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

Personalised recommendations