Transport of a hydrophilic compound into the cerebrospinal fluid during experimental allergic encephalomyelitis and after lipopolysaccharide administration.
OBJECTIVE
The transport of the hydrophilic model compound sodium fluorescein into the cerebrospinal fluid (CSF) of rats was studied during experimental allergic encephalomyelitis (EAE), as a model for local central nervous system (CNS) inflammatory disease, and after a single injection of a pyrogenic dose of lipopolysaccharide (LPS), as a model for a general inflammation.


METHODS
Transport of sodium fluorescein was measured by means of serial CSF and plasma sampling. Transport of this hydrophilic model compound was studied in Lewis rats suffering from EAA and three hours after LPS administration in male Wistar rats.


RESULTS
During acute EAE, sodium fluorescein concentrations in the CSF increased twofold compared to control animals, whereas plasma kinetics were comparable within both groups. After i.v. LPS administration, however, plasma as well as CSF kinetic parameters of sodium fluorescein concentration were significantly changed from those seen in control animals. Transport of sodium fluorescein from plasma into the CSF was calculated as the ratio Area Under the Curve (AUC)CSF/AUCPLASMA. During acute EAE this ratio increased 2-fold compared to control animals, whereas after i.v. LPS administration it was not significantly different from the one obtained in control animals.


CONCLUSIONS
These results suggest an opening of the blood-brain barrier (BBB) during a cerebral inflammatory response, like acute EAE, but not after LPS administration.
de Vries
H E
HE
Leiden/Amsterdam Center for Drug Research, University of Leiden, Netherlands.
Eppens
E F
EF
Prins
M
M
Kuiper
J
J
van Berkel
T J
TJ
de Boer
A G
AG
Breimer
D D
DD
D000818:Animals; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism* / Q000503:physiopathology; D019793:Fluorescein; D005452:Fluoresceins / Q000493:pharmacokinetics*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D005452:Fluoresceins; D008070:Lipopolysaccharides; D019793:Fluorescein