Blood–Brain Barrier Permeability to Sodium. Modification by Glucose or Insulin?

Publisher Website
Google Scholar
Abstract
In order to explore the pathogenetic mechanism underlying the changes in blood‐brain barrier sodium transport in experimental diabetes, the effects of hyperglycemia and of hypoinsulinemia were studied in nondiabetic rats. In untreated diabetes, the neocortical blood‐brain barrier permeability for sodium decreased by 20% (5.6 ± 0.7 versus 7.0 ± 0.8 × 105 ml/g/s) as compared to controls. Intravenous infusion of 50% glucose for 2 h was associated with a decrease in the blood‐brain barrier permeability to sodium (5.4 ± 1.2 × 105 ml/g/s), whereas rats treated with an inhibitor of insulinsecretion (SMS 201–995, a somatostatin‐analogue) had normal sodium permeability (7.3 ± 2.0 × 105 ml/g/s). Acute insulin treatment of diabetic rats normalized the sodium permeability within a few hours as compared to a separate control group (7.7 ± 1.1 versus 6.9 ± 1.4 × 105 ml/g/s). To elucidate whether the abnormal blood‐brain barrier passage is caused by a metabolic effect of glucose or by the concomitant hyperosmolality, rats were made hyperosmolar by intravenous injection of 50% mannitol. Although not statistically significant, blood‐brain barrier sodium permeability increased in hyperosmolar rats as compared to the control rats (8.3 ± 1.0 and 7.0 ± 1.9 × 105 ml/g/s, respectively). It is concluded that either hyperglycemia per se or a glucose metabolite is responsible for the blood‐brain barrier abnormality which occurs in diabetes. Further, we suggest that the specific decrease of sodium permeability could be the result of glucose‐mediated inhibition of the Na+K+‐ATPase localized at the blood‐brain barrier.