Glial regulation of the blood-brain barrier in health and disease

Abstract

The brain is the organ with the highest metabolic demand in the body. Therefore, it needs specialized vasculature to provide it with the necessary oxygen and nutrients, while protecting it against pathogens and toxins. The blood-brain barrier (BBB) is very tightly regulated by specialized endothelial cells, two basement membranes, and astrocytic endfeet. The proximity of astrocytes to the vessel makes them perfect candidates to influence the function of the BBB. Moreover, other glial cells are also known to contribute to either BBB quiescence or breakdown. In this review, we summarize the knowledge on glial regulation of the BBB during development, in homeostatic conditions in the adult, and during neuroinflammatory responses.

Multifaceted interactions between adaptive immunity and the central nervous system

“…For a cell to penetrate the meningeal vessels and enter the CSF, it has to cross the BMB. The BMB differs from the BBB and lacks some of the latter’s components, such as astrocyte endfeet (64, 65), making it easier for cells to penetrate (Fig. 2, A and B).…”

Paving the Way Toward Complex Blood-Brain Barrier Models Using Pluripotent Stem Cells

“…Remarkably, the APOE protein, of which isoform 4 (APOE4) is a major risk factor for AD, is expressed in the endfeet of astrocytes [100]. Deletion of APOE in mice, in fact, leads to BBB breakdown, as displayed by increased leakage of dye into the brain of APOE-deficient mice compared with wild-type mice [101], and this difference increases with age [102].…”

Plasminogen and its fragments in rat brain: a plausible role for astrocytes in angiostatin generation

“…Several lines of investigation show that astrocytes play a regulatory role for endothelial functions. Perivascular astrocytes are thought to control the induction and maintenance of endothelial BBB phenotype [17]. Astrocytes participate directly and actively in capillary formation in the brain.…”

“…In respect of this, astrocytes are of particular interest due to the three reasons: 1) astrocytes are the most frequent cells in the CNS, which emulate the metabolic activity of neurons; 2) astrocytes play a pivo tal role as "communicators" between neurons and endotheliocytes; 3) astrocytes have been shown to produce and release several negative regulators of angiogenesis, i.e. endostatins, and have all the necessary proteinase and enzyme cascades to decompose Pg to yield angiostatins [17,19,20]. So far, there are no data available on this function of brain astrocytes.…”