4-TRIMETHYLAMMONIUM ANTIPYRINE - A QUATERNARY AMMONIUM NONRADIONUCLIDE MARKER FOR BLOOD-BRAIN-BARRIER INTEGRITY DURING INVIVO MICRODIALYSIS

被引:33
作者
ALLEN, DD
CROOKS, PA
YOKEL, RA
机构
[1] UNIV KENTUCKY,MED CTR,COLL PHARM,PHARM BLDG,ROSE ST,LEXINGTON,KY 40536
[2] UNIV KENTUCKY,GRAD CTR TOXICOL,LEXINGTON,KY 40536
关键词
MICRODIALYSIS; BLOOD BRAIN BARRIER INTEGRITY; NONRADIONUCLIDE BLOOD BRAIN BARRIER MARKER; INTERNAL REFERENCE; 4-TRIMETHYLAMMONIUM ANTIPYRINE;
D O I
10.1016/1056-8719(92)90074-B
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The well-controlled microdialysis (MD) study of substance permeation into brain extracellular fluid (ECF) and cerebrospinal fluid requires consideration of blood-brain barrier (BBB) integrity, which might be compromised by microdialysis probe implantation. Others have assessed BBB integrity with radionuclide markers. A nonradionuclide marker may be desirable in many studies. A charged antipyrine analogue may be useful to determine BBB integrity with concomitant antipyrine characterization of probe efficiency (Yokel et al., 1992, J Pharmacol Toxicol Methods 27:135-142), and may not require another analytical technique. We synthesized, validated, and evaluated 4-trimethylammonium antipyrine (4TMA-AP) as a BBB integrity marker. BBB permeation was determined by calculation of a BBB integrity percentage (P(i)) from brain/blood concentrations. The P(i)s of Evan's blue, which does not permeate the intact BBB, and 4TMA-AP were not significantly different in rats without known BBB disruption, suggesting a lack of 4TMA-AP permeation through the intact BBB. When MD probes were slowly implanted into the frontal cortex, 4TMA-AP P(i)s were usually zero. Intracarotid oleic acid injection to open the BBB significantly increased 4TMA-AP P(i)s, suggesting that 4TMA-AP entered brain ECF when the BBB was compromised. Rapid probe implantation produced increased 4TMA-AP P(i)s, suggesting BBB disruption. The predicted appearance of 4TMA-AP in brain ECF suggests that it is a BBB integrity marker.
引用
收藏
页码:129 / 135
页数:7
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