Neuroprotective drug development in stroke: blood pressure and its impact

IMPORTANCE OF BLOOD PRESSURE IN STROKE RESEARCH: From the experimental animal to man, blood pressure is the most important physiologic variable in stroke research. Acutely, after the onset of stroke, modest alterations in arterial pressure are the major determinant of cerebral blood flow to the tissue at risk and ultimately of the anatomical extent of infarction. Whether in animals or man, moderate drug-induced hypotension counteracts the brain protection afforded by even the most powerful anti-ischaemic drugs, the discovery of which has transformed stroke research in the last decade. Chronic hypertension is strongly associated with stroke risk in man whereas anti-ischaemic drug development has been based on normotensive animals with limited use of genetically (or surgically induced) hypertensive animals. ADVANCES IN STROKE RESEARCH: Major advances have taken place in stroke research in recent years. These include the development of pharmacological approaches which are peculiar to the brain (modulation of excitotoxicity) or which are common to many vascular beds (flow enhancement strategies using calcium entry blockers or endothelin receptor antagonists). It is clear that blood pressure is particularly important for all aspects of brain ischaemia research, both in animals and man.