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Into rather unexplored terrain—transcellular transport across the blood–brain barrier
Author(s) -
De Bock Marijke,
Van Haver Valérie,
Vandenbroucke Roosmarijn E.,
Decrock Elke,
Wang Nan,
Leybaert Luc
Publication year - 2016
Publication title -
glia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.954
H-Index - 164
eISSN - 1098-1136
pISSN - 0894-1491
DOI - 10.1002/glia.22960
Subject(s) - paracellular transport , transcellular , blood–brain barrier , biology , microbiology and biotechnology , tight junction , endocytosis , caveolae , transcytosis , endothelium , neuroscience , pinocytosis , vesicular transport protein , septate junctions , endosome , adherens junction , intracellular , gap junction , central nervous system , signal transduction , vesicle , cell , permeability (electromagnetism) , biochemistry , membrane , cadherin , endocrinology
Efficient neuronal signaling in the central nervous system strictly depends on a well‐balanced microenvironment around glial cells, synapses, and axons. Unique features of the blood–brain barrier (BBB) endothelium largely determine the composition of this micro‐milieu and are dependent on the tight interplay with surrounding astrocytes and pericytes. BBB endothelial cells are endowed with a highly restrictive junctional complex that occludes the intercellular cleft, thereby preventing paracellular diffusion. The paracellular pathway is subject to extensive research as integrity loss of the junctional complex is associated with many neuropathologies, inflammation, and edema. Another important feature of the BBB endothelium is the low prevalence of nonspecific, transcytotic events, including (macro)pinocytosis, clathrin‐dependent and caveolin‐dependent endocytosis and the subsequent trafficking of vesicles to the opposite membrane. Although less studied, evidence is accruing that this pathway importantly contributes to increased BBB permeability, often when the junctional complex remains intact. Here, we review current knowledge on the contribution of the transcellular pathway to the BBB leak observed in different pathologic conditions. In addition, we hypothesize that nonselective, large pore connexin and pannexin channels may contribute to transcellular transport, either by providing a direct diffusion pathway across the endothelial monolayer, or indirectly, by exerting control over intracellular levels of the signaling ion Ca 2+ that is involved in many steps of the vesicular pathway. We conclude that transcytotic events at the BBB, despite being less acknowledged, cannot be simply dismissed as done in the past, but actively contribute to BBB leakage in many different pathologies. GLIA 2016;64:1097–1123