Animal Models of Stroke Versus Clinical Stroke: Comparison of Infarct Size, Cause, Location, Study Design, and Efficacy of Experimental Therapies

Victoria E. O'Collins*, Geoffrey A. Donnan, Malcolm R. Macleod, David W. Howells

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapter

Abstract

A quantitative and qualitative comparison of contemporary neuroprotection and thrombolytic stroke trials and their preclinical animal counterparts has been undertaken, with meta-analysis (DerSimonian and Laird, 1986) used to evaluate imaging and histological outcomes.Results from 35 clinical trials including 5,532 patients were compared with data from 3,145 pre-clinical acute-stroke experiments in 45,476 animals. While clinical trials tended to be of higher methodological quality and have larger sample sizes than animal experiments (71 patients vs. 7 animals per group), both were similarly underpowered owing to the greater variability in human stroke (average standard deviation of mean in humans 99% v 30% in animals). Proportionally, animal infarcts were almost four times larger than human infarcts in untreated control groups (27% v 8% of the hemisphere) although there was considerable variability in size owing to comorbidities and stroke type. Eighty-six percent of animal studies and 54% of clinical trials reported smaller infarcts in groups receiving treatment, with 41% of clinical trials reporting an improvement in the pre-specified hypothesis. Animal experiments were not effective in predicting individual trial results, nor the level of neuroprotection, however, there was a fair agreement between the direction of the animal and clinical outcomes when looking at the overall direction of drug outcome. As a drug screening tool, experimental stroke studies need refinement. Rational frameworks for translational research will help.

Original languageEnglish
Title of host publicationAnimal Models for the Study of Human Disease
PublisherElsevier Inc.
Pages531-568
Number of pages38
ISBN (Print)9780124158948
DOIs
Publication statusPublished - Jul 2013

Keywords

  • Animal models
  • Cerebral ischemia
  • Focal ischemia
  • Infarct size
  • Meta-analysis
  • Neuroprotection
  • Stroke
  • Thrombolysis

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