The blood-brain barrier (BBB) is a diffusion barrier, which impedes influx of most
compounds from blood to brain. Three cellular elements of the brain microvasculature
compose the BBB-endothelial cells, astrocyte end-feet, and pericytes (PCs). Tight
junctions (TJs), present between the cerebral endothelial cells, form a diffusion
barrier, which selectively excludes most blood-borne substances from entering the
brain. Astrocytic end-feet tightly ensheath the vessel wall and appear to be critical
for the induction and maintenance of the TJ barrier, but astrocytes are not believed
to have a barrier function in the mammalian brain. Dysfunction of the BBB, for example,
impairment of the TJ seal, complicates a number of neurologic diseases including stroke
and neuroinflammatory disorders. We review here the recent developments in our understanding
of the BBB and the role of the BBB dysfunction in CNS disease. We have focused on
intraventricular hemorrhage (IVH) in premature infants, which may involve dysfunction
of the TJ seal as well as immaturity of the BBB in the germinal matrix (GM). A paucity
of TJs or PCs, coupled with incomplete coverage of blood vessels by astrocyte end-feet,
may account for the fragility of blood vessels in the GM of premature infants. Finally,
this review describes the pathogenesis of increased BBB permeability in hypoxia-ischemia
and inflammatory mechanisms involving the BBB in septic encephalopathy, HIV-induced
dementia, multiple sclerosis, and Alzheimer disease.