Reintroduction of the Rat for Experimental Subarachnoid Hemorrhage with Accelerated Clot Formation: A Low Mortality Model with Persistent Clots as a Precondition for Studies in Vasospasm

Angelika Ehlert; Ulrich Budde; Ralf Middendorff; Gerd Manthei; Andre Kemmling; Bastian Tiemann

doi:10.1055/s-0038-1641561

Journal of Neurological Surgery Part A: Central European Neurosurgery, Table of Contents

J Neurol Surg A Cent Eur Neurosurg 2018; 79(05): 424-433
DOI: 10.1055/s-0038-1641561

Technical Note

Georg Thieme Verlag KG Stuttgart · New York

Reintroduction of the Rat for Experimental Subarachnoid Hemorrhage with Accelerated Clot Formation: A Low Mortality Model with Persistent Clots as a Precondition for Studies in Vasospasm

Authors

Angelika Ehlert

¹Department of Neurosurgery, Asklepios Klinik St. Georg Hamburg, Hamburg, Germany
Ulrich Budde

²Department of Haemostasiologie, Asklepios Klinik Altona, Hamburg, Germany
Ralf Middendorff

³Department of Anatomy and Cell Biology, University of Giessen, Giessen, Hessen, Germany
Gerd Manthei

¹Department of Neurosurgery, Asklepios Klinik St. Georg Hamburg, Hamburg, Germany
Andre Kemmling

⁴Department of Neuroradiology, Universitätsklinikum Schleswig-Holstein, Campus Lübeck, Lübeck, Hamburg, Germany

⁵Department of Neuroradiology, Universitätsklinikum Hamburg Eppendorf Klinik und Poliklinik fur Neuroradiologische Diagnostik und Intervention, Hamburg, Germany
Bastian Tiemann

⁶Versuchstierheilkunde, University Hospital of Hamburg, Hamburg, Germany

Abstract

Background Cerebral vasospasm as a delayed, possibly treatable sequel of subarachnoid hemorrhage (SAH) is a focus of experimental animal research. For this purpose, the rat is not a good model because of the difficulty creating a stable subarachnoid clot that persists > 1 to 2 days and could induce vasospasm. Only in rat models with a high mortality of ∼ 50% or more can SAH and its effects be investigated. Therefore, other animals than rodents are used for investigating the delayed effects of SAH. Only animal studies addressing the acute effects of SAH use rats.

Objective We designed a model that allows intensive clot formation combined with low mortality to facilitate studies on the delayed effects of experimental SAH, for example, delayed vasospasm or other alterations of vessels.

Methods After in vitro acceleration of the clotting process in the rats' blood by tissue factor and preliminary in vivo testing, we induced a SAH by injecting blood together with tissue factor in 22 rats. We analyzed clot expansion, length of clot persistence, chronic alterations, and histologic changes.

Results The injection of blood supplemented by tissue factor led to persistent voluminous blood clots in the subarachnoid space close to the large arteries. Despite the pronounced SAH, all animals survived, allowing investigation of delayed SAH effects. All animals killed within the first 7 days after surgery had extensive clots; in some animals, the clots remained until postoperative day 12. During further clot degradation connective tissue appeared, possibly as a precursor of SAH-related late hydrocephalus.

Conclusion The injection of blood together with tissue factor significantly improves SAH induction in the rat model. This rat model allows studying delayed SAH effects as found in humans.

Keywords

subarachnoid hemorrhage - rat model - cerebral vasospasm - clot induction - low mortality

Full Text

References

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