Robinson P J, Rapoport S I
Am J Physiol. 1987 Sep;253(3 Pt 2):R459-66. doi: 10.1152/ajpregu.1987.253.3.R459.
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.
最近的实验表明,在渗透性打开血脑屏障后,它对大分子的重新闭合速度比对小分子的更快。对渗透性打开血脑屏障后不同时间不同大小分子的血脑屏障通透性进行的定量理论分析支持了由于内皮细胞间紧密连接打开而形成孔隙的概念。实验还表明,在打开屏障后10分钟内,有大量水以约1.6×10⁻⁴立方厘米×秒⁻¹×克脑⁻¹的平均速率从毛细血管流入脑内。提出了一个基于孔隙形成以及大量流体流动的血脑屏障通透性数学模型,该模型适用于圆柱形孔隙和矩形缝隙。实验数据与大约200埃的孔隙半径或大约220埃的缝隙宽度相符。在屏障打开6分钟时,计算得出膜表面每200平方微米约有1个孔隙的孔隙密度,随着屏障重新闭合,孔隙密度略有降低。计算得出的大量流体流动在屏障打开35分钟内降低了一个数量级,并且是血脑屏障通透性改变的一个主要因素。渗透性打开血脑屏障后血脑屏障通透性的大小依赖性表明与囊泡运输增强不相符。