Non-invasive measurement of solute permeability in cerebral microvessels of the rat

To quantify the solute permeability of rat cerebral microvessels, we measured the apparent permeability (P) of pial microvessels to various sized solutes. The pial microcirculation was observed by a high numerical aperture objective lens through a section of the frontoparietal bone thinned with a micro-grinder (a revised method from Easton and Fraser, 1994, J Physiol. 475:147–157, 1994). Sodium fluorescein (MW 376) at concentration 0.1 mg/ml or FITC-dextrans (MW 4k, 10k, 20k, 40k, 70k) at concentration 1 mg/ml in 1% BSA mammalian Ringer, was introduced into the cerebral circulation via the ipsilateral carotid artery by a syringe pump at a constant rate of ~ 3 ml/min. P was determined using a highly sensitive quantitative fluorescence imaging and analyzing method. The mean P to sodium fluorescein was 2.71 (± 0.76 SD, n = 11) × 10− 6 cm/s. The mean P to FITC-dextrans were 0.92 (± 0.46 SD, n = 10) × 10− 6 cm/s for Dextran-4k, 0.31 (± 0.13 SD, n = 7) × 10− 6 cm/s for Dextran-10k, 0.24 (± 0.10 SD, n = 6) × 10− 6 cm/s for Dextran-20k, 0.19 (± 0.11 SD, n = 10) × 10− 6 cm/s for Dextran-40k, and 0.15 (± 0.05 SD, n = 11) × 10− 6 cm/s for Dextran-70k. These values were 1/10 to 1/6 of those of rat mesenteric microvessels for similar sized solutes (Fu, B.M., Shen, S., 2004. Acute VEGF effect on solute permeability of mammalian microvessels in vivo. Microvasc. Res. 68, 51–62.).