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Meta-Analysis
. 2013 Apr 1:14:41.
doi: 10.1186/1471-2202-14-41.

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

Jakob O Ström  1 , Edvin Ingberg, Annette Theodorsson, Elvar Theodorsson
Affiliations
Meta-Analysis

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

Jakob O Ström et al. BMC Neurosci. .

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.

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Figures

Figure 1
Figure 1
When analyses were saturated, 1430 articles had been evaluated for inclusion in the meta-analysis. After exclusion due to criteria A-G, 346 studies, describing 502 control groups, remained. Due to lack of certain pieces of information in some of the articles, not all 502 control groups could be included in all four multiple regression analyses, as shown in the thick-boarded boxes to the right in the figure.
Figure 2
Figure 2
The choice of strain significantly affected the Infarct size coefficient of variation, so that the Wistar rendered lower variability than Sprague Dawley, which was chosen as the reference category. The Other strains category increased variability in comparison to Sprague Dawley. Regarding mortality rate, the effects of animal strain was limited to a slight decrease from using SHR. N = 469 and 351, respectively, in the two analyses/graphs. The bars represent 0.95 confidence intervals.
Figure 3
Figure 3
Concerning Infarct size coefficient of variation, the general trend was that the intraluminal filament procedure, here chosen to be the reference category, resulted in lower percentages than did the other methods. The emboli and endothelin injection methods rendered significantly higher variability. Mortality rate was clearly influenced by choice of induction procedure, with higher percentages in the emboli studies, while the direct and endothelin procedures had decreased numbers of deaths in comparison to the intraluminal filament method. N = 469 and 351, respectively, in the two analyses/graphs. The bars represent 0.95 confidence intervals.
Figure 4
Figure 4
Silicone coated filaments rendered lower infarct size coefficient of variation than the uncoated filaments. Poly-L-Lysine coated and other filaments resulted in infarct size coefficients of variation comparable to the uncoated counterparts. No effect on Mortality rate from the choice of intraluminal filament type was seen. N = 383 and 265, respectively, in the two analyses/graphs. The bars represent 0.95 confidence intervals.
Figure 5
Figure 5
Frequencies of registered categories in the 502 included control groups. The specific exclusion criteria are presented separately in the last 4 bars. Many of the variable names are abbreviated in the figure; for extended description, see Table 1. “Histology” in the bar “Type of infarct evaluation” refers to acidic/basic stain or silver stain histology. EEG = Electroencephalography, B = Blood, Hb = Hemoglobin.
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