Quantitative evaluation of the effect of propylene glycol on BBB permeability

Abstract

To establish the blood-brain barrier (BBB) blocking property of propylene glycol (PG) using the (14)C sucrose technique, quantitatively evaluate the effect of PG on BBB permeability using an MRI technique based on graphical analysis, and demonstrate the sensitivity of MRI for testing newer investigational drugs. Brain uptake of sucrose was measured in treated (PG+) and untreated (PG-) rats using a (14)C sucrose technique in rat brains (N = 10) that had undergone two hours of middle cerebral artery occlusion (MCAO) and three hours of reperfusion. Another group of PG+ and PG- rats (N = 8) underwent MRI. T2-weighted (T2W) and diffusion-weighted (DW) images were acquired on a 4.7T MR system. A rapid T1 mapping protocol was implemented to acquire a baseline data set followed by postinjection data sets at regular intervals. The data were postprocessed pixelwise to generate permeability coefficient color maps. A significant (P < 0.05) reduction in (14)C sucrose space was observed on the ischemic side of PG+ rats only. Permeability coefficient estimates obtained by MRI from the ipsilateral hemisphere in PG+ rats were significantly lower than those in PG- rats (P < 0.05). There was no significant change on the contralateral side in PG+ rats. The results show that PG protects the BBB in ischemic stroke, and MRI measurements are sufficiently sensitive to noninvasively detect small drug effects. MRI is useful for evaluating the BBB blocking effect of PG in an ischemic stroke model of rat brain. The results from the MR experiment agree well with findings from the (14)C sucrose technique.