Size selectivity of blood-brain barrier permeability at various times after osmotic opening

Abstract

Recent experiments have shown that after osmotic opening the blood-brain barrier recloses more rapidly to larger than to smaller molecules. Quantitative theoretical analysis of blood-brain barrier permeability to different-sized molecules at different times after osmotic opening supports the concept of pore creation as a result of opening of tight junctions between endothelial cells. Experiments also suggest significant bulk water flow from capillaries into brain within 10 min after opening at an average rate of approximately 1.6 X 10(-4) cm3 X s-1 X g brain-1. A mathematical model of blood-brain barrier permeability based on the creation of pores, together with bulk fluid flow, is presented for both cylindrical pores and rectangular slits. Experimental data are compatible with pore radii of approximately 200 A or slit widths of approximately 220 A. Pore densities of approximately 1 pore per 200 microns 2 of membrane surface are calculated at 6 min after barrier opening, reducing slightly as the barrier recloses. Calculated bulk flow is reduced by an order of magnitude within 35 min of barrier opening and is a major factor in altered blood-brain barrier permeability. Size dependence of blood-brain barrier permeability following osmotic opening is shown to be incompatible with enhanced vesicular transport.