Predicting experimental success: a retrospective case-control study using the rat intraluminal thread model of stroke

Disease Models & Mechanisms, vol. 13

Abstract

The poor translational success rate of preclinical stroke research may partly be due to inaccurate modelling of the disease. We provide data on transient middle cerebral artery occlusion (tMCAO) experiments, including detailed intraoperative monitoring to elaborate predictors indicating experimental success (ischemia without occurrence of confounding pathologies). The tMCAO monitoring data (bilateral cerebral blood flow, CBF; heart rate, HR; and mean arterial pressure, MAP) of 16 animals with an 'ideal' outcome (MCA-ischemia), and 48 animals with additional or other pathologies (subdural haematoma or subarachnoid haemorrhage), were checked for their prognostic performance (receiver operating characteristic curve and area under the curve, AUC). Animals showing a decrease in the contralateral CBF at the time of MCA occlusion suffered from unintended pathologies. Implementation of baseline MAP, in addition to baseline HR (AUC, 0.83, 95% c.i. 0.68 to 0.97), increased prognostic relevance (AUC, 0.89, 95% c.i. 0.79 to 0.98). Prediction performance improved when two additional predictors referring to differences in left and right CBF were considered (AUC, 1.00, 95% c.i. 1.0 to 1.0). Our data underline the importance of peri-interventional monitoring to verify a successful experimental performance in order to ensure a disease model as homogeneous as possible.

Authors 8

1. Lisa Liebenstund Aachen

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

   University Hospital Aachen 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

2. Mark Coburn Aachen

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

   University Hospital Aachen 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

3. Christina Fitzner Aachen 3CARE

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   3CARE 2 , , , , D-52047 Aachen , Germany

   Cardiovascular Critical Care & Anesthesia Research 2 , , , , D-52047 Aachen , Germany

   RWTH Aachen University 2 , , , , D-52047 Aachen , Germany

   Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

   University Hospital Aachen 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

   University Hospital Aachen 2 , , , , D-52047 Aachen , Germany

   3CARE, Cardiovascular Critical Care & Anesthesia Research, University Hospital Aachen, RWTH Aachen University, D-52047 Aachen, Germany

4. Antje Willuweit

   Forschungszentrum Jülich

   Affiliation as printed

   Forschungszentrum Jülich GmbH 3 , , D-52428 Jülich , Germany

   Institute of Neuroscience and Medicine, Medical Imaging Physics (INM-4) 3 , , D-52428 Jülich , Germany

5. Karl‐Josef Langen Aachen Department of Nuclear Medicine

   Forschungszentrum Jülich · Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Forschungszentrum Jülich GmbH 3 , , D-52428 Jülich , Germany

   Institute of Neuroscience and Medicine, Medical Imaging Physics (INM-4) 3 , , D-52428 Jülich , Germany

   RWTH Aachen University 4 Department of Nuclear Medicine , , , D-52047 Aachen , Germany

   University Hospital Aachen 4 Department of Nuclear Medicine , , , D-52047 Aachen , Germany

   Department of Nuclear Medicine, University Hospital Aachen, RWTH Aachen University, D-52047 Aachen, Germany

6. Jingjin Liu Aachen

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   Rheinisch-Westfälische Technische Hochschule (RWTH) Aachen University 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

   University Hospital Aachen 1 Department of Anesthesiology , , , D-52074 Aachen , Germany

7. Michael Veldeman Aachen Department of Neurosurgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University 5 Department of Neurosurgery , , , D-52047 Aachen , Germany

   University Hospital Aachen 5 Department of Neurosurgery , , , D-52047 Aachen , Germany

   Department of Neurosurgery, University Hospital Aachen, RWTH Aachen University, D-52047 Aachen, Germany

8. Anke Höllig Aachen Department of Neurosurgery

   Universitätsklinikum Aachen · RWTH Aachen University

   Affiliation as printed

   RWTH Aachen University 5 Department of Neurosurgery , , , D-52047 Aachen , Germany

   University Hospital Aachen 5 Department of Neurosurgery , , , D-52047 Aachen , Germany

   Department of Neurosurgery, University Hospital Aachen, RWTH Aachen University, D-52047 Aachen, Germany