Molecular modulation of the blood-brain barrier during stroke

Stroke is the third leading cause of death and a leading cause of long-term disability in Western civilization (1). During stroke, a decrease in oxygen levels (hypoxia) due to a cessation in blood fiow and an increase in cerebral vascular permeability and vasogenic cerebral edema occur, which contribute to neurological deficits associated with brain infarct (2). Most of what is known about the effects of stroke on the brain is in neurons. Ischemic stroke is known to cause neuronal cell death and alter the cellular activity of neurons. The ultimate goal of stroke research is the development of therapeutic agents, which will improve patient clinical outcome. Most stroke research currently investigates the cellular mechanisms associated primarily with neuronal damage. Additionally, a majority of these therapies aim at reducing neurological deficit by modulating neuronal intracellular mechanisms. While this research is compelling, recent research investigating ischemia/reperfusion implicates blood-brain barrier (BBB) integrity as a primary factor in the clinical outcome of stroke patients. It has become increasingly clear that the BBB plays an important role in the pathophysiology of several conditions including stroke, human immunodeficiency virus (HIV) dementia, experimental autoimmune encephalomyelitis (EAE), and infiammation (3-7). It is now known that the extent of BBB dysfunction has profound effects on pathophysiologies associated with the central nervous system.