Transport of GM1 and GM1 inner ester across an in vitro model of the blood-brain barrier.
Gangliosides, especially GM1, attenuate the in vivo damage caused by various neurotoxins. The chemically neutral inner ester of GM1 may be a better cytoprotective agent against some neurotoxins than the parent GM1 compound, because it may cross the blood-brain barrier (BBB) more easily than the anionic GM1. Using an in vitro bovine brain endothelial cell model of the BBB, we show the inner ester more readily transverse the tight junction barrier of this model than does GM1. Further, it is demonstrated that the GM1 inner ester is stable for several hours at pH values between 7.0 and 8.2 at 37 degrees C. Finally, the results illustrate that the BBB model may be useful for testing other gangliosides and their various derivatives for increased ability to cross the BBB.
GRECC, ENRM VA Hospital, Bedford, MA 01730, USA.
J M
JM
Wells
R F
RF
Ventura
P B
PB
Eisenhauer
D C
DC
McKenna
R E
RE
Fine
M D
MD
Ullman
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001812:Blood-Brain Barrier; D002417:Cattle; D004727:Endothelium / Q000166:cytology / Q000378:metabolism; D004952:Esters / Q000378:metabolism; D005677:G(M1) Ganglioside / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007700:Kinetics; D008959:Models, Neurological; D051381:Rats; D019108:Tight Junctions / Q000378:metabolism
D004952:Esters; D005677:G(M1) Ganglioside