Water permeabilities of neural cells and capillaries in brain : Using claudin-5 knocked out mice and H-1 MRI

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The water permeability of capillaries and neural cells in the brain were analyzed by using claudin-t knocked out mice and H-1 MRI. The anatomic basis for blood-brain barrier (BBB) resides in tight junctions (TJs) of brain endothelial cells in addition to their limited transcytosis. The claudin-5 was identified as a major TJ cell adhesion molecule in brain endothelial cells. Three relaxation reagents (ca. 700Da - 17kDa) were applied to estimate water permeability of the neurons/glia cells and BBB in mice. In the intact mice, the longitudinal relaxation rates (1/T_1) showed minimal changes (<0.1 s^<-1>) even the 1/T_1 of blood water was accelerated more than 40 s^<-1> by using the 3 reagents. It is suggested that the normal BBB have very low water permeability. In the claudin-5 knocked out mice, Gd-DTPA^<2-> can pass through the modified BBB. From the dose-dependency of Gd-DTPA, a water efflux rate from the neurons/glia cells was detected which is corresponding to a diffusional water permeability of 1.5-1.0cm s^<-1>. The relaxation reagents (bigger than 2kDa) could not pass through the modified BBB. From the dose-dependency of a relaxation reagent, a water efflux rate from the BBB was detected which is corresponding to a moderate range of diffusional water permeability. These findings provide a new insight on the molecular biology of BBB, and also represent usefulness of this method to monitor physiological parameters of genetically modified animals.