A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subar

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ORIGINAL ARTICLE

A Systematic and Meta-Analysis of Mortality in Experimental Mouse Models Analyzing Delayed Cerebral Ischemia After Subarachnoid Hemorrhage Marcel A. Kamp 1 & Jasper H. van Lieshout 1 & Maxine Dibué-Adjei 1,2 & Jasmin K. Weber 1 & Toni Schneider 2 & Tanja Restin 3,4 & Igor Fischer 5 & Hans-Jakob Steiger 1

Received: 26 September 2016 / Revised: 23 November 2016 / Accepted: 27 November 2016 # Springer Science+Business Media New York 2017

Abstract Animal models are established to display the pathophysiological changes following subarachnoid hemorrhage (SAH). The aim of the present study was to determine case fatality in mouse delayed cerebral ischemia (DCI) models, to compare mortality in mouse DCI models to case fatality in human SAH patients, and to identify factors influencing mouse mortality. A systematic search of the PubMed database was performed to identify all studies that assessed mouse DCI models. Mortality rates and predictor variables were extracted and compared to the human case fatality after SAH as previously reported. Predictors for mouse mortality were identified through multivariate analysis. Forty-eight studies were included in the quantitative analysis. The mean overall mortality rate was 21% in mouse DCI models. However, the time Electronic supplementary material The online version of this article (doi:10.1007/s12975-016-0513-3) contains supplementary material, which is available to authorized users. * Marcel A. Kamp [email protected]

1

Department of Neurosurgery, Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany

2

Institute for Neurophysiology, Medical Faculty, University of Cologne, Robert-Koch-Str. 39, 50931 Köln, Germany

3

Zurich Center for Integrative Human Physiology, Institute of Physiology, University of Zurich, Winterthurerstrasse 190, 8057 Zurich, Switzerland

4

Institute of Anesthesiology, University Hospital Zurich, Rämistrasse 100, 8091 Zurich, Switzerland

5

Division of Informatics and Statistics, Department of Neurosurgery, Medical Faculty, Heinrich Heine University, Moorenstraße 5, 40225 Düsseldorf, Germany

period between induction of SAH and evaluation of mortality rates is a significant variable influencing the mortality rate in mouse SAH models. The experimental SAH model was the only significant predictor for mouse mortality after 48 h. In contrast, neither the genetic background nor the anesthetic changed the case fatality rate. Mouse mortality at 24, 48, and 72 h after experimental SAH in DCI models was significantly lower than human case fatality following aneurysmal SAH. The mean overall mortality rate in mouse DCI models is significantly lower than human case fatality following aneurysmal SAH. However, time between SAH induction and evaluation is a significant variable influencing the mortality rate in mouse SAH models. Further analyses will be required to establish whether and to which extent different DCI models affect mortality and reflect human pathophysiology. Keywords Subarachno