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

Abstract

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.).