A cell culture model of the blood-brain barrier.
Endothelial cells that make up brain capillaries and constitute the blood-brain barrier become different from peripheral endothelial cells in response to inductive factors found in the nervous system. We have established a cell culture model of the blood-brain barrier by treating brain endothelial cells with a combination of astrocyte-conditioned medium and agents that elevate intracellular cAMP. These cells form high resistance tight junctions and exhibit low rates of paracellular leakage and fluid-phase endocytosis. They also undergo a dramatic structural reorganization as they form tight junctions. Results from these studies suggest modes of manipulating the permeability of the blood-brain barrier, potentially providing the basis for increasing the penetration of drugs into the central nervous system.
Rubin
L L
LL
Athena Neurosciences, Inc., South San Francisco, California 94080.
Hall
D E
DE
Porter
S
S
Barbu
K
K
Cannon
C
C
Horner
H C
HC
Janatpour
M
M
Liaw
C W
CW
Manning
K
K
Morales
J
J
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001692:Biological Transport; D001812:Blood-Brain Barrier; D002417:Cattle; D002478:Cells, Cultured; D002999:Clone Cells; D003470:Culture Media; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004705:Endocytosis; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007150:Immunohistochemistry; D007365:Intercellular Junctions / Q000378:metabolism; D007700:Kinetics; D008954:Models, Biological; D051381:Rats
D003470:Culture Media; D000242:Cyclic AMP; D006152:Cyclic GMP