期刊
THROMBOSIS RESEARCH
卷 105, 期 5, 页码 447-453出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/S0049-3848(02)00050-6
关键词
heparin-derived oligosaccharides; pharmacodynamics; distribution; brain; CSF
资金
- NATIONAL INSTITUTE ON AGING [R41AG015740] Funding Source: NIH RePORTER
- NIA NIH HHS [1R41 AG15740-01] Funding Source: Medline
Although heparin-derived oligosaccharide(s) (HDO) have been clinically used for the management of neurological disorders, such as stroke and Alzheimer's disease (AD), very little information on the mechanism of their therapeutic action is known. To test the hypothesis that HDO may pass through the blood-brain barrier (BBB) to mediate their effects, a pharmacodynamic (PD) model was developed and the presence of HDO in the cerebrospinal fluid (CSF) was used as a BBB accessibility index. Rats were treated with an ultralow molecular weight (MW) heparin fragment C3 via the intravenous or subcutaneous routes at 5-10 mg/kg. At varying periods, the plasma, CSF, and brain samples were collected, and functional anti-factor Xa activities were measured to quantitate the CSF/plasma ratios (CPR) and the brain uptake. C3 showed CPR of 1.7% and 0.8% after intravenous and subcutaneous injections, respectively. These findings were verified by intravenous administration of tritium-labeled C3 followed by detection of the radioactivity in the CSF and brain homogenates. These data suggest that ultralow MW HDO may pass through the BBB. (C) 2002 Published by Elsevier Science Ltd.
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