Multimodal severity assessment using objective and quantitative indicators in a rat cisterna magna subarachnoid hemorrhage model

Experimental Neurology, vol. 405, pp. 115938

Abstract

Assessing and minimizing animal distress is a critical ethical and scientific aspect of preclinical research. The EU Directive 2010/63 requires an assessment of the overall burden of animal experimentation in order to refine procedures and establish humane endpoints. Despite this, there is still a lack of validated, objective, and quantitative indicators for a comprehensive assessment of severity. This study uses a multimodal approach to objectively quantify distress in Wistar rats (n = 98) following subarachnoid hemorrhage (SAH) induced by cisterna magna injection using different injection volumes and speeds. Clinical parameters (score sheets, neuroscore), behavioral measures (voluntary wheel running, open field, burrowing), and biochemical markers (fecal corticosterone metabolites, FCMs) were assessed up to 10 days after surgery. The results show that all of the intervention groups, including the sham-operated animals, experienced a significant initial deterioration, with a prolonged recovery in the SAH groups. Behavioral activity was significantly reduced postoperatively, with delayed recovery in SAH animals compared to sham-operated animals. FCM levels were elevated in the early postoperative period, reflecting acute stress responses. Principal component analysis identified open field parameters as key contributors to severity scores, highlighting their potential as objective stress indicators. This study underscores the necessity of model-specific severity assessments, demonstrating that a multimodal approach enhances the accuracy of evaluation. Integrating objective behavioral and physiological indicators can refine animal models in neurological research. Future studies should explore advanced scoring systems to further optimize welfare assessment in experimental SAH models.

Authors 6

1. Laura Warner corresponding Aachen Translational Neurosurgery and Neurobiology Department of Neurosurgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Translational Neurosurgery and Neurobiology, Department of Neurosurgery, University Hospital, Medical Faculty, RWTH Aachen University, Aachen, Germany. Electronic address: lwarner@ukaachen.de

2. Ekaterina Harder Aachen Translational Neurosurgery and Neurobiology Department of Neurosurgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Translational Neurosurgery and Neurobiology, Department of Neurosurgery, University Hospital, Medical Faculty, RWTH Aachen University, Aachen, Germany

3. Annika Bach-Hagemann

   Fraunhofer Institute for Toxicology and Experimental Medicine

   Affiliation as printed

   Fraunhofer Institute for Toxicology and Experimental Medicine, Department of Preclinical Pharmacology and Toxicology, Hannover, Germany

4. Lisa Josephine Korn Aachen Translational Neurosurgery and Neurobiology Department of Neurosurgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Translational Neurosurgery and Neurobiology, Department of Neurosurgery, University Hospital, Medical Faculty, RWTH Aachen University, Aachen, Germany

5. Rupert Palme

   University of Veterinary Medicine Vienna

   Affiliation as printed

   Experimental Endocrinology, Department of Biomedical Sciences and Pathobiology, University of Veterinary Medicine, Vienna, Austria

6. Ute Lindauer Aachen Translational Neurosurgery and Neurobiology Department of Neurosurgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Translational Neurosurgery and Neurobiology, Department of Neurosurgery, University Hospital, Medical Faculty, RWTH Aachen University, Aachen, Germany