Transport of a hydrophilic compound into the cerebrospinal fluid during experimental allergic encephalomyelitis and after lipopolysaccharide administration

被引:19
作者
deVries, HE [1 ]
Eppens, EF [1 ]
Prins, M [1 ]
Kuiper, J [1 ]
vanBerkel, TJC [1 ]
deBoer, AG [1 ]
Breimer, DD [1 ]
机构
[1] LEIDEN UNIV,LEIDEN AMSTERDAM CTR DRUG RES,DIV BIOPHARMACEUT,SYLVIUS LABS,2300 RA LEIDEN,NETHERLANDS
关键词
multiple sclerosis; experimental allergic encephalomyelitis; lipopolysaccharide; blood-brain barrier;
D O I
10.1023/A:1016291806357
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Purpose. 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) / AUC(PLASMA). 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.
引用
收藏
页码:1932 / 1936
页数:5
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