Changes in the glucose transporter of brain capillaries

1992 ◽  
Vol 70 (S1) ◽  
pp. S113-S117 ◽  
Author(s):  
Sami I. Harik

Brain capillary endothelium has a high density of the GLUT-1 facilitative glucose transporter protein. This is reasonable in view of the brain's high metabolic rate for glucose and its isolation behind unique capillaries with blood – brain barrier properties. Thus, the brain endothelium, which constitutes less than 0.1% of the brain weight, has to transport glucose for the much larger mass of surrounding neurons and glia. I describe here the changes that occur in the density of glucose transporters in brain capillaries of subjects with Alzheimer disease, where there is a decreased cerebral metabolic rate for glucose, and in a novel clinical entity characterized by defective glucose transport at the blood – brain barrier. In subjects with Alzheimer disease, cerebral microvessels showed a marked decrease in the density of the glucose transporter when compared with age-matched controls, but there was no change in the density of glucose transporters in erythrocyte membranes. Thus, I believe that the decreased density of glucose transporters in the brains of subjects with Alzheimer disease is the result rather than the cause of the disease. In contradistinction, the primary defect in glucose transport at the blood – brain barrier in subjects with the recently described entity is associated with decreased density of GLUT-1 in erythrocyte membranes.Key words: brain microvessels, capillary endothelium, blood – brain barrier, glucose transporter, Alzheimer disease, hypoglycorrhachia.

1995 ◽  
Vol 15 (4) ◽  
pp. 681-686 ◽  
Author(s):  
Sylvia Rahner-Welsch ◽  
Johannes Vogel ◽  
Wolfgang Kuschinsky

The association of glucose transporters (GLUT1) and brain capillaries was tested in different brain structures of rats by a direct comparison of the topologies of capillaries and GLUT1 in identical brain sections. Antibody staining of capillaries (fibronectin) and GLUT1 were made visible by fluorescence microscopy. The results showed differences between brain structures containing a tight and a leaky blood–brain barrier. All capillaries of brain structures with a tight blood–brain barrier showed congruent staining of GLUT1 and capillary morphology. The circumventricular organs that are known to have leaky barrier capillaries were stained by fibronectin antibodies but not by GLUT1 antibodies. Ependymal cells showed moderate staining by GLUT1 antibodies both in areas with tight and leaky barriers. The subcommissural organ appeared to be unique showing neither capillary nor GLUT1 stain. It is concluded that glucose transporters (GLUT1) exist in all brain capillaries of blood–brain barrier structures, whereas they are absent in leaky barrier structures. Moderate amounts of glucose transporter (GLUT1) can also be detected in ependymal cells.


2018 ◽  
Vol 132 (3) ◽  
pp. 361-374 ◽  
Author(s):  
Patrizia Giannoni ◽  
Jerome Badaut ◽  
Cyril Dargazanli ◽  
Alexis Fayd’Herbe De Maudave ◽  
Wendy Klement ◽  
...  

The cerebrovasculature is a multicellular structure with varying rheological and permeability properties. The outer wall of the brain capillary endothelium is enclosed by pericytes and astrocyte end feet, anatomically assembled to guarantee barrier functions. We, here, focus on the pericyte modifications occurring in disease conditions, reviewing evidence supporting the interplay amongst pericytes, the endothelium, and glial cells in health and pathology. Deconstruction and reactivity of pericytes and glial cells around the capillary endothelium occur in response to traumatic brain injury, epilepsy, and neurodegenerative disorders, impacting vascular permeability and participating in neuroinflammation. As this represents a growing field of research, addressing the multicellular reorganization occurring at the outer wall of the blood-brain barrier (BBB) in response to an acute insult or a chronic disease could disclose novel disease mechanisms and therapeutic targets.


1996 ◽  
Vol 284 (3) ◽  
pp. 355-365 ◽  
Author(s):  
Sylvia Bolz ◽  
Catherine L. Farrell ◽  
Klaus Dietz ◽  
Hartwig Wolburg

Author(s):  
Benjamin P. Heithoff ◽  
Kijana K. George ◽  
Aubrey N. Phares ◽  
Ivan A. Zuidhoek ◽  
Carmen Munoz-Ballester ◽  
...  

AbstractIn the adult brain, multiple cell types are known to produce factors that regulate blood-brain barrier properties, including astrocytes. Yet several recent studies disputed a role for mature astrocytes at the blood-brain barrier. To determine if astrocytes contribute a non-redundant and necessary function in maintaining the adult blood-brain barrier, we used a mouse model of tamoxifen-inducible astrocyte ablation. In adult mice, tamoxifen induction caused sparse apoptotic astrocyte cell death within 2 hours. Indicative of BBB damage, leakage of the small molecule Cadaverine and the large plasma protein fibrinogen into the brain parenchyma indicative of BBB damage was detected as early as astrocyte ablation was present. Vessels within and close to regions of astrocyte loss had lower expression of the tight junction protein zonula occludens-1 while endothelial glucose transporter 1 expression was undisturbed. Cadaverine leakage persisted for several weeks suggesting a lack of barrier repair. This is consistent with the finding that ablated astrocytes were not replaced. Adjacent astrocytes responded with partial non-proliferative astrogliosis, characterized by morphological changes and delayed phosphorylation of STAT3, which restricted dye leakage to the brain and vessel surface areas lacking coverage by astrocytes one month after ablation. In conclusion, astrocytes are necessary to maintain blood-brain barrier integrity in the adult brain. Blood-brain barrier-regulating factors secreted by other cell types, such as pericytes, are not sufficient to compensate for astrocyte loss.Main PointsMature astrocytes are necessary for maintenance of endothelial tight junctions in the adult brain. Ablated astrocytes are not replaced by proliferation or process extension of neighboring astrocytes resulting in long-term blood-brain barrier damage.


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