Diffusion of docosahexaenoic and eicosapentaenoic acids through the blood-brain barrier: an in situ cerebral perfusion study.

Abstract Docosahexaenoic (DHA) and eicosapentaenoic (EPA) acids are n-3 polyunsaturated fatty acids with a therapeutic potential for CNS diseases. Here, using an in situ brain perfusion technique in mice, we show that [ 14 C]-DHA and [ 14 C]-EPA readily cross the mouse blood–brain barrier (BBB) with brain transport coefficients (Clup) of 48 ± 3 μl g −1  s −1 and 52 ± 4 μl g −1  s −1 , respectively. Mechanical capillary depletion of brain homogenates showed that less than 10% of [ 14 C]-DHA or [ 14 C]-EPA remained in endothelial cells of the brain vasculature, demonstrating that both molecules fully crossed the BBB. Addition of bovine serum albumin decreased the Clup of [ 14 C]-DHA to 0.6 ± 0.3 μl g −1  s −1 , indicating that binding to albumin reduced importantly, but not totally, the passage of DHA through the BBB. The Clup of [ 14 C]-DHA or [ 14 C]-EPA was not saturable at concentration up to 100 μM, suggesting that these compounds crossed the BBB by simple diffusion. However, long-term high-DHA dietary consumption reduced the Clup of [ 14 C]-DHA to 33 ± 6 μl g −1  s −1 (−20%, p