Neural precursor cell influences on blood-brain barrier characteristics in rat brain endothelial cells.
This study explores the effects of neural precursor cells (NPCs) on barrier characteristics in brain vasculature. Primary rat brain endothelial cells were exposed to conditioned medium from NPCs isolated from day 14 embryonic rat brains and maintained as free-floating undifferentiated neurospheres. Such exposure increased brain endothelial transcript levels of the mdr1a but not mdr1b gene encoding P-glycoprotein (Pgp) and reduced proliferation but did not alter transendothelial resistance (TER). These effects were compared to those seen following co-culture with differentiating NPCs or with primary astrocytes. NPCs, if grown adherent, differentiate into glial and neuronal cells as assessed by immunocytochemical and mRNA analysis. Brain endothelial cells when co-cultured with these cells also showed reduced proliferation and enhanced mdr1a expression, but in addition increased TER. Similar increases were observed in co-culture with astrocytes. These results suggest that undifferentiated NPCs produce factors that influence Pgp expression whereas their progeny also affect tight junction integrity.
Lim
Joseph C
JC
Department of Pharmacology, University of Cambridge, Tennis Court Road, Cambridge CB2 1PD, UK.
Wolpaw
Adam J
AJ
Caldwell
Maeve A
MA
Hladky
Stephen B
SB
Barrand
Margery A
MA
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000378:metabolism; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism; D018528:ATP-Binding Cassette Transporters / Q000378:metabolism; D000818:Animals; D001253:Astrocytes / Q000502:physiology; D001921:Brain / Q000166:cytology*; D002454:Cell Differentiation / Q000502:physiology*; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques / Q000379:methods; D017077:Culture Media, Conditioned / Q000494:pharmacology; D004622:Embryo, Mammalian; D042783:Endothelial Cells / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D008297:Male; D009474:Neurons / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D013234:Stem Cells / Q000502:physiology*; D014316:Tritium / Q000493:pharmacokinetics; D014750:Vincristine / Q000493:pharmacokinetics
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018528:ATP-Binding Cassette Transporters; D017077:Culture Media, Conditioned; D014316:Tritium; D014750:Vincristine; C095122:multidrug resistance protein 3