Enhancement of blood-brain barrier permeability by sodium caprate

We examined the effect of sodium caprate on the integrity of the tight junc tions of brain capillary endothelial cells, using a modified in-situ brain perfusion technique. Model hydrophilic compounds used were [H-3]mannitol, [ C-14]sucrose, [H-3]PE [H-3]PEG4000, FITC-dextran 4000, FITC-dextran 20 000 and FITC-dextran 70 000. The brain distribution volume of [C-14]sucrose was significantly increased by sodium caprate in a concentration-dependent manner. The effective minimu m concentration was 10 mM. Furthermore, the effects of sodium caprate on th e distribution volumes of hydrophilic compounds, [H-3]mannitol, [C-14]sucro se, [H-3]PEG900, [H-3]PEG4000, FITC-dextran 4000, FITC-dextran 20 000 and F ITC-dextran 70 000, showed a molecular weight dependence. A plot of apparen t permeation clearance against diffusion coefficient values suggested that 20 mM sodium caprate induced pores so large that the above compounds could pass through the blood-brain barrier with negligible friction within the po re. Our results showed that intracarotid sodium caprate perfusion could enhance the permeation of hydrophilic compounds through the blood-brain barrier.