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Transfer Constants for Blood-Brain Barrier Permeation of the Neuroexcitatory Shellfish Toxin, Domoic Acid

Published online by Cambridge University Press:  18 September 2015

Edward Preston  and
Ivo Hynie
Edward Preston*
Affiliation:
Division of Biological Sciences, National Research Council of Canada, and the Laboratory Centre for Disease Control, Health and Welfare, Canada, Ottawa
Ivo Hynie
Affiliation:
Division of Biological Sciences, National Research Council of Canada, and the Laboratory Centre for Disease Control, Health and Welfare, Canada, Ottawa
*
Division of Biological Sciences, Bldg. M54, National Research Council, Ottawa, Ontario, Canada K1A 0R6
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Abstract:

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The cause of the toxic mussel poisoning episode in 1987 was traced to a plankton-produced excitotoxin, domoic acid. Experiments were undertaken to quantitate the degree to which blood-borne domoic acid can permeate the microvasculature to enter the brain. Pentobarbital-anesthetized, adult rats received an i.v. injection of 3H-domoic acid which was permitted to circulate for 3-60 min. Transfer constants (Ki) describing blood-to-brain diffusion of tracer were calculated from analysis of the relationship between brain vs plasma radioactivity with time. Mean values (mL.g-1.s-1 x 106) for permeation into 7 brain regions (n = 10 rats) ranged from 1.60 ± 0.13 (SE) to 1.86 ± 0.33 (cortex, ponsmedulla respectively), and carrier transport or regional selectivity in uptake were not evident. Nephrectomy prior to domoic acid injection resulted in the elevation of circulating plasma tracer level and brain uptake. The Ki values are comparable to those for other polar compounds such as sucrose, and indicate that the blood-brain barrier greatly limits the amount of toxin that enters the brain. Together with absorbed dosage, integrity of the cerebrovascular barrier and normal kidney function are important to the outcome of accidentally ingesting domoic acid.

Type
Original Articles
Information
Canadian Journal of Neurological Sciences , Volume 18 , Issue 1 , February 1991 , pp. 39 - 44
Copyright
Copyright © Canadian Neurological Sciences Federation 1991

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