Cerebral cortical capillary basement membrane thickening in galactosaemic rats

Summary Wistar-Kyoto rats fed a diet containing 30% by weight galactose for 15–21 months developed significant thickening of the endothelial basement membranes of capillaries from the frontal cortex of the cerebrum, by comparison with cerebral capillary basement membranes from animals on a standard diet (p<0.001), or animals receiving a diet containing 30% galactose together with 250 mg/kg diet of the aldose reductase inhibitor, Sorbinil (0.001<p<0.01). The effect was similar to that which we have reported previously in the retinal capillaries of these animals. Spontaneously hypertensive rats on the high-galactose diet showed modest cerebral capillary basement membrane thickening (0.02<p<0.05) only for one of the measurement protocols utilised, and the process was not prevented by Sorbinil. Biochemical assays of retina, cerebral cortex, and blood serum from Wistar-Kyoto and spontaneously hypertensive rats maintained on the Sorbinil regimen showed that the drug did cross the blood-retinal and blood-brain barriers. Similar to our previous study on the retinal capillaries, we observed no degeneration of pericyte or endothelial cell cytoplasm, and no alteration in the pericyte/endothelial cell nuclear ratio in the cerebral capillaries of galactosaemic animals, by comparison with controls. Based on immunocytochemical studies in the human retina, it has been claimed that aldose reductase is present in capillary pericytes but absent in the endothelial cells. However, we observe a considerably smaller pericyte/ endothelial cell nuclear ratio in the capillaries of the cerebral cortex of the rat, by comparison with those of the retina. Also, pericyte coverage of the cerebral cortical capillaries is much less than that of the retinal capillaries of these animals. Therefore, it appears that the biochemical process(es) responsible for basement membrane thickening are unlikely to reside within the pericytes.