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Into rather unexplored terrain : transcellular transport across the blood-brain barrier

Marijke De Bock (UGent) , Valérie Van Haver (UGent) , Roosmarijn Vandenbroucke (UGent) , Elke Decrock (UGent) , Nan Wang (UGent) and Luc Leybaert (UGent)
(2016) GLIA. 64(7). p.1097-1123
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Abstract
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 non-specific, 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 non-selective, 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 Ca2+ 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 contributes BBB leakage in many different pathologies.
Keywords
calcium, P2X7, connexin, pannexin, Brain endothelial cells, transcytosis, CAPILLARY ENDOTHELIAL-CELLS, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, CLATHRIN-INDEPENDENT ENDOCYTOSIS, RECEPTOR-MEDIATED TRANSCYTOSIS, HUMAN SUBCUTANEOUS FIBROBLASTS, GAP-JUNCTION HEMICHANNELS, INHIBITS SEIZURE ACTIVITY, CALCIUM-DEPENDENT MANNER, INTERCELLULAR CA2+ WAVES, NIGRIVENTER SPIDER VENOM

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Chicago
De Bock, Marijke, Valerie Van Haver, Roosmarijn Vandenbroucke, Elke Decrock, Nan Wang, and Luc Leybaert. 2016. “Into Rather Unexplored Terrain : Transcellular Transport Across the Blood-brain Barrier.” Glia 64 (7): 1097–1123.
APA
De Bock, Marijke, Van Haver, V., Vandenbroucke, R., Decrock, E., Wang, N., & Leybaert, L. (2016). Into rather unexplored terrain : transcellular transport across the blood-brain barrier. GLIA, 64(7), 1097–1123.
Vancouver
1.
De Bock M, Van Haver V, Vandenbroucke R, Decrock E, Wang N, Leybaert L. Into rather unexplored terrain : transcellular transport across the blood-brain barrier. GLIA. 2016;64(7):1097–123.
MLA
De Bock, Marijke, Valerie Van Haver, Roosmarijn Vandenbroucke, et al. “Into Rather Unexplored Terrain : Transcellular Transport Across the Blood-brain Barrier.” GLIA 64.7 (2016): 1097–1123. Print.
@article{7147181,
  abstract     = {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 non-specific, 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 non-selective, 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 Ca2+ 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 contributes BBB leakage in many different pathologies.},
  author       = {De Bock, Marijke and Van Haver, Val{\'e}rie and Vandenbroucke, Roosmarijn and Decrock, Elke and Wang, Nan and Leybaert, Luc},
  issn         = {0894-1491},
  journal      = {GLIA},
  language     = {eng},
  number       = {7},
  pages        = {1097--1123},
  title        = {Into rather unexplored terrain : transcellular transport across the blood-brain barrier},
  url          = {http://dx.doi.org/10.1002/glia.22960},
  volume       = {64},
  year         = {2016},
}

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