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Open Access Highly Accessed Methodology article

Method parameters’ impact on mortality and variability in rat stroke experiments: a meta-analysis

Jakob O Ström1*, Edvin Ingberg1, Annette Theodorsson12 and Elvar Theodorsson1

Author Affiliations

1 Department of Clinical and Experimental Medicine, Clinical Chemistry, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden

2 Department of Clinical and Experimental Medicine, Neurosurgery, Faculty of Health Sciences, Linköping University, County Council of Östergötland, Linköping, Sweden

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BMC Neuroscience 2013, 14:41  doi:10.1186/1471-2202-14-41

Published: 1 April 2013

Abstract

Background

Even though more than 600 stroke treatments have been shown effective in preclinical studies, clinically proven treatment alternatives for cerebral infarction remain scarce. Amongst the reasons for the discrepancy may be methodological shortcomings, such as high mortality and outcome variability, in the preclinical studies. A common approach in animal stroke experiments is that A) focal cerebral ischemia is inflicted, B) some type of treatment is administered and C) the infarct sizes are assessed. However, within this paradigm, the researcher has to make numerous methodological decisions, including choosing rat strain and type of surgical procedure. Even though a few studies have attempted to address the questions experimentally, a lack of consensus regarding the optimal methodology remains.

Methods

We therefore meta-analyzed data from 502 control groups described in 346 articles to find out how rat strain, procedure for causing focal cerebral ischemia and the type of filament coating affected mortality and infarct size variability.

Results

The Wistar strain and intraluminal filament procedure using a silicone coated filament was found optimal in lowering infarct size variability. The direct and endothelin methods rendered lower mortality rate, whereas the embolus method increased it compared to the filament method.

Conclusions

The current article provides means for researchers to adjust their middle cerebral artery occlusion (MCAo) protocols to minimize infarct size variability and mortality.

Keywords:
Brain infarction; Middle cerebral artery occlusion; Rats; Methods; Mortality; Variability