Abstract:
:All extant vertebrates have a blood-brain barrier (BBB), a specialized layer of cells that controls molecular traffic between blood and brain, and contributes to the regulation (homeostasis) of the brain microenvironment. Such homeostasis is critical for the stable function of synapses and neural networks. The barrier is formed by vascular endothelial cells in most groups, but by perivascular glial cells (astrocytes) in elasmobranch fish (sharks, skates, and rays). It has been unclear which is the ancestral form, but this information is important, as it could offer insights into the roles of the endothelium and perivascular glia in the modern mammalian BBB. We have used electron microscopic techniques to examine three further ancient fish groups, with intravascular horseradish peroxidase as permeability tracer. We find that in bichir and lungfish the barrier is formed by brain endothelial cells, while in sturgeon it is formed by a complex perivascular glial sheath, but with no detectable tight junctions. From their BBB pattern, and position on the vertebrate family tree, we conclude that the ancestral vertebrate had a glial BBB. This means that an endothelial barrier would have arisen independently several times during evolution, and implies that an endothelial barrier gave strong selective advantage. The selective advantage may derive partly from greater separation of function between endothelium and astrocytic glia. There are important implications for the development, physiology, and pathology of the mammalian BBB, and for the roles of endothelium and glia in CNS barrier layers.
journal_name
Gliajournal_title
Gliaauthors
Bundgaard M,Abbott NJdoi
10.1002/glia.20642subject
Has Abstractpub_date
2008-05-01 00:00:00pages
699-708issue
7eissn
0894-1491issn
1098-1136journal_volume
56pub_type
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