Review
The influence of stroke risk factors and comorbidities on assessment of stroke therapies in humans and animals
Sandeep Ankolekar,
Sarah Rewell,
David W. Howells,
Philip M. W. Bath,
Sandeep Ankolekar
Stroke Trials Unit, University of Nottingham, Nottingham, UK
Search for more papers by this authorSarah Rewell
Florey Neuroscience Institutes, Melbourne Brain Centre, Heidelberg, Australia
Search for more papers by this authorDavid W. Howells
Florey Neuroscience Institutes, Melbourne Brain Centre, Heidelberg, Australia
Search for more papers by this authorCorresponding Author
Philip M. W. Bath
Stroke Trials Unit, University of Nottingham, Nottingham, UK
Correspondence: Philip M. W. Bath, Division of Stroke, University of Nottingham, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK.
E-mail: [email protected]
Search for more papers by this authorSandeep Ankolekar,
Sarah Rewell,
David W. Howells,
Philip M. W. Bath,
Sandeep Ankolekar
Stroke Trials Unit, University of Nottingham, Nottingham, UK
Search for more papers by this authorSarah Rewell
Florey Neuroscience Institutes, Melbourne Brain Centre, Heidelberg, Australia
Search for more papers by this authorDavid W. Howells
Florey Neuroscience Institutes, Melbourne Brain Centre, Heidelberg, Australia
Search for more papers by this authorCorresponding Author
Philip M. W. Bath
Stroke Trials Unit, University of Nottingham, Nottingham, UK
Correspondence: Philip M. W. Bath, Division of Stroke, University of Nottingham, City Hospital Campus, Hucknall Road, Nottingham NG5 1PB, UK.
E-mail: [email protected]
Search for more papers by this authorConflicts of interests: D. H., P. B., S. A., and S. R. have no conflicts of interest.
Funding: P. B. is Stroke Association Professor of Stroke Medicine. S. A. is funded by the Medical Research Council (grant G0501797). D. H. is Acting Director of the National Stroke Research Institute and recipient of NHMRC Program, Fellowship and Project Grants.
Abstract
The main driving force behind the assessment of novel pharmacological agents in animal models of stroke is to deliver new drugs to treat the human disease rather than to increase knowledge of stroke pathophysiology. There are numerous animal models of the ischaemic process and it appears that the same processes operate in humans. Yet, despite these similarities, the drugs that appear effective in animal models have not worked in clinical trials. To date, tissue plasminogen activator is the only drug that has been successfully used at the bedside in hyperacute stroke management. Several reasons have been put forth to explain this, but the failure to consider comorbidities and risk factors common in older people is an important one. In this article, we review the impact of the risk factors most studied in animal models of acute stroke and highlight the parallels with human stroke, and, where possible, their influence on evaluation of therapeutic strategies.
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