DYSFUNCTION OF CHOLINE TRANSPORT-SYSTEM THROUGH BLOOD-BRAIN-BARRIER IN STROKE-PRONE SPONTANEOUSLY HYPERTENSIVE RATS

The blood-brain barrier (BBB) transport of choline was compared between stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar KY rats (WKY). The permeability surface area product (PS) of [3H]choline through the BBB in SHRSP (3.03 × 10-3 ± 1.09 × 10-3 ml/min/g brain) was significantly lower than that in WKY (7.23 × 10-3 ± 0.97 × 10-3 ml/min/g brain) in the presence of respective rat sera. No significant difference in the brain vascular space was indicated from the apparent uptake of [3H] sucrose between SHRSP and WKY. There was no significant difference for the Michaelis constant of choline transport between SHRSP (262 ± 97 μm) and WKY (180 ± 32 μm). However, the maximum velocity in SHRSP (3.41 ± 1.19 nmol/min/g brain) was 37% lower than in WKY (5.40 ± 0.38 nmol/min/g brain). Brain microdialysis technique was employed to collect the brain interstitial fluid in the rat hippocampus. The concentration of free choline in the brain dialysate in SHRSP was about half of that in WKY, while no significant difference was observed for the plasma concentration of free choline between SHRSP and WKY. In contrast, no significant difference was observed for the transport of D-[3H]glucose, 3-methyl-[3H]D-glucose and [3H]-phenylalanine through the BBB between SHRSP and WKY. Accordingly, the decreased choline concentration in the brain interstitial fluid ascribed to the specific dysfunction of the BBB choline transport has been demonstrated in SHRSP. © 1990, The Pharmaceutical Society of Japan. All rights reserved.