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71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

21.06. - 24.06.2020

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Haem degradation products after subarachnoid haemorrhage cause long-term vasoconstriction and vessel wall thickening of extraparenchymal brain arteries in mice

Hämabbauprodukte nach einer Subarachnoidalblutung induzieren eine Verengung und Gefäßwandverdickung extraparenchymaler Hirnarterien von Mäusen

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  • presenting/speaker Alexander Joerk - Universitätsklinikum Jena, Klinik für Neurologie, Jena, Deutschland; Universitätsklinikum Jena, Else Kröner-Forschungskolleg AntiAge, Jena, Deutschland
  • presenting/speaker Sophie Charlotte Schröder - Universitätsklinikum Jena, Klinik für Neurologie, Jena, Deutschland; Universitätsklinikum Jena, Else Kröner-Promotionskolleg JSAM, Jena, Deutschland
  • Marcel Ritter - Friedrich-Schiller-Universität Jena, Institut für Anorganische und Analytische Chemie, Jena, Deutschland
  • Diana Freitag - Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland
  • Ina Ingrisch - Universitätsklinikum Jena, Klinik für Neurologie, Jena, Deutschland
  • Daniel Schulze - Friedrich-Schiller-Universität Jena, Institut für Anorganische und Analytische Chemie, Jena, Deutschland
  • Georg Pohnert - Friedrich-Schiller-Universität Jena, Institut für Anorganische und Analytische Chemie, Jena, Deutschland
  • Matthias Westerhausen - Friedrich-Schiller-Universität Jena, Institut für Anorganische und Analytische Chemie, Jena, Deutschland
  • Rolf Kalff - Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland
  • Otto Wilhelm Witte - Universitätsklinikum Jena, Klinik für Neurologie, Jena, Deutschland; Universitätsklinikum Jena, Else Kröner-Forschungskolleg AntiAge, Jena, Deutschland; Universitätsklinikum Jena, Else Kröner-Promotionskolleg JSAM, Jena, Deutschland
  • Jan Walter - Universitätsklinikum Jena, Klinik für Neurochirurgie, Jena, Deutschland
  • Knut Holthoff - Universitätsklinikum Jena, Klinik für Neurologie, Jena, Deutschland

Deutsche Gesellschaft für Neurochirurgie. 71. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), 9. Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie. sine loco [digital], 21.-24.06.2020. Düsseldorf: German Medical Science GMS Publishing House; 2020. DocV201

doi: 10.3205/20dgnc197, urn:nbn:de:0183-20dgnc1979

Published: June 26, 2020

© 2020 Joerk 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/.

Outline

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Objective: Delayed cerebral ischemia (DCI) caused by symptomatic cerebral vasospasm is the most important preventable cause of mortality and poor neurological outcome in subarachnoid haemorrhage (SAH) patients. We hypothesize that haem degradation products (HDPs), originating from the intracranial haematoma after aneurysm rupture, are involved in pathogenesis of delayed cerebral vasospasm by BK potassium channel inhibition. HDPs, comprising propentdyopents (PDP) and bilirubin oxidation products (BOX), are present in the cerebrospinal fluid of aneurysmal SAH patients and induced a short-onset vasoconstriction of cerebral arterioles in preclinical mouse models.

Methods: To study the long-term effect of HDPs on diameter and wall morphology of cerebral arteries, SAH was induced experimentally in adult wildtype and BK channel deficient mice (FVB/N) by the subarachnoid injection of autologous blood or PDP/BOX isomers into the cisterna magna. After the postinterventional days 7 or 14, mouse brains were removed and postfixed in 4% PFA for at least 48h. Subsequently, the diameter and vessel wall thickness of cross-sectioned artery segments in 40 µm brain slices were analyzed by confocal laser scanning microscopy after immunofluorescent staining with DAPI, anti-smooth muscle actin (SMA) and anti-CD 31.

Results: Two weeks after the subarachnoid injection of venous autologous blood (30µl, n=5), PDP or BOX isomers (each 30µl, 1µM, n=5) the extraparenchymal located basilar artery (BA) and posterior communicating artery (PCA) were affected by a significant (p<0.05) increase of smooth muscle wall thickness in adult wildtype mice in comparison to control (n=4). This vessel wall remodelling was absent in PDP-treated BK knockout mice (30µl, 1µM, n=4). In addition, the wall thickness of the intraparenchymal located azygos pericallosal artery (APA) remained unchanged in all experimental groups (p>0.05). Focused on the diameter, blood as well as HDPs induced a significant vasoconstriction of PCA vessel segments in wildtype mice in comparison to control.

Conclusion: Besides the short-onset vasoactivity of HDPs, our data demonstrate for the first time a long-term vessel wall remodelling of brain base arteries which correlates in time with the onset of delayed vasospasm in SAH patients. In addition, the morphology changes were limited exclusively to extraparenchymal arteries and dependent on BK channel expression. These findings may promote to a better pathomechanistic understanding of cerebral vasospasm.