The influence of stroke risk factors and comorbidities on assessment of stroke therapies in humans and animals.
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.
Stroke Trials Unit, University of Nottingham, Nottingham, UK.
Sandeep
S
Ankolekar
Sarah
S
Rewell
David W
DW
Howells
Philip M W
PM
Bath
D000367:Age Factors; D000428:Alcohol Drinking / Q000009:adverse effects; D000818:Animals; D001281:Atrial Fibrillation / Q000150:complications; D003925:Diabetic Angiopathies / Q000209:etiology; D004195:Disease Models, Animal; D004285:Dogs; D006801:Humans; D006937:Hypercholesterolemia / Q000150:complications; D006973:Hypertension / Q000150:complications; D051379:Mice; D011817:Rabbits; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects; D020521:Stroke / Q000208:ethnology / Q000209:etiology*