Permeability of Blood-brain Barrier to Various Sized Molecules

We studied disruption of the blood-brain barrier (BBB) by acute hypertension and a hyperosmolar solution. The goals were to determine whether 1) disruption of the BBB occurs primarily in arteries, capillaries, or veins, and 2) transport of different-sized molecules is homogeneous or size dependent. Sprague-Dawley rats were studied using intravital fluorescent microscopy of pial vessels and fluorescein-labeled dextrans (FITC-dextran, mol wt = 70,000, 20,000, and 4,000 daltons). The site of disruption was determined by the appearance of microvascular leaky sites. Transport of different-sized molecules was calculated from clearance of FITC-dextran. During gradual hypertension and osmotic disruption, all leaky sites were venular. Rapid hypertension produced venular leaky sites and, in some experiments, diffuse arteriolar extravasation of FITC-dextran. Clearance of different-sized molecules was homogeneous during acute hypertension. In contrast, clearance of molecules during osmotic disruption was size dependent. The findings suggest that 1) venules and veins are the primary sites of disruption following acute hypertension and a hyperosmolar solution; 2) transport of different-sized molecules is homogeneous following acute hypertension, which suggests a vesicular mechanism; and 3) transport following hyperosmolar disruption is size dependent, which suggests that hyperosmolar disruption may involve formation of pores as well as vesicular transport.