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Previous studies showing downregulation of blood-brain barrier (BBB) glucose-transporter activity in vivo in experimental diabetes have recently been questioned. Therefore, our investigations examined both the BBB glucose-transporter activity in experimental diabetes in vivo, with the use of the in situ internal carotid artery perfusion technique, and the microvessel glucose-transporter concentration, with quantitative Western immunoblots. These studies show that BBB glucose-transporter activity in vivo is decreased 44% in experimental diabetes (blood glucose concn 443 +/- 12 mg/dl), parallel with a 44% decrease in cerebral blood flow, a normal brain blood volume, and a 75% prolongation of capillary transit time. The glucose-transporter concentration is decreased 77 +/- 9% in microvessels isolated from diabetic rat brain compared with controls, as measured by quantitative Western blotting. These studies confirm the original observations that the BBB glucose transporter is downregulated in experimental diabetes, in association with a parallel decrease in cerebral blood flow. In addition, these studies, in conjunction with other recent experiments from this laboratory showing elevated glucose-transporter mRNA in diabetic rat brain capillaries, suggest the primary mechanism underlying the downregulation is a posttranscriptional inhibition of glucose-transporter mRNA translation.

Two classes of pericytes are thought to exist in cerebral microvasculature, granular and agranular. This classification is based on the presence or absence of cytoplasmic, lysosome-like granules of variable size and appearance. The pericytes in structurally normal human brain tissue from 17 patients, male and female, ranging in age from 14 to 77, were examined. Light microscopic examination of single sections revealed that 67% of pericyte profiles contained granules in both sexes, and this ratio did not change with age. Following the serial reconstructions of 80 individual pericytes, it was found that all contained characteristic cytoplasmic granules. These data show that if truly agranular pericytes do exist in human cerebral microvasculature, they must constitute less than 5% of the population.

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