Preservation of transendothelial glucose transporter 1 and P-glycoprotein transporters in a cortical slice culture model of the blood-brain barrier.
A variety of neurological diseases are characterized by disturbances of the blood-brain barrier (BBB) and its transporters. We recently introduced fibroblast growth factor treated cortical organotypic slice cultures of mice as a model for in vitro studies of the blood-brain barrier and have now further characterized the maintenance and function of transport-proteins typically expressed in the endothelium of cerebral blood vessels. The glucose transporter GLUT-1 is present in blood vessels of slice cultures derived from postnatal day 4 to 21 mice after 3 days in vitro. The endothelial multidrug resistance P-glycoprotein (P-gp) which is involved in the control of pharmacological substance transport across the blood-brain barrier is also maintained in blood vessels, most prominently in slice cultures derived from postnatal day 14 and 21 mice. To assess P-gp function, we tested rhodamine 123 transport in presence or absence of the P-gp inhibitor verapamil. Rhodamine 123-fluorescence accumulated rapidly in the vascular lumen both in acute slices and in slices cultured for 3 days in vitro. Our results provide evidence that endothelial transporters and their functional properties can be maintained in organotypic cortical slices cultures, thus making it an attractive model system for the study of the blood-brain barrier.
Camenzind
R S
RS
Section of Functional Neuroanatomy, Institute of Anatomy, Department of Biomedicine, University of Basel, Pestalozzistrasse 20, CH-4056 Basel, Switzerland.
Chip
S
S
Gutmann
H
H
Kapfhammer
J P
JP
Nitsch
C
C
Bendfeldt
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D001812:Blood-Brain Barrier / Q000378:metabolism*; D002540:Cerebral Cortex / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D009924:Organ Culture Techniques
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D051272:Glucose Transporter Type 1