All vertebrates started out with a glial blood-brain barrier 4-500 million years ago

TY - JOUR

T1 - All vertebrates started out with a glial blood-brain barrier 4-500 million years ago

AU - Bundgaard, Magnus

AU - Abbott, N. Joan

PY - 2008/5

Y1 - 2008/5

N2 - 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. (c) 2008 Wiley-Liss, Inc.

AB - 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. (c) 2008 Wiley-Liss, Inc.

KW - fish

KW - evolution

KW - brain blood vessels

KW - horseradish peroxidase

KW - tracer

KW - astrocyte

KW - basal lamina

KW - CUTTLEFISH SEPIA-OFFICINALIS

KW - ASTROCYTE-ENDOTHELIAL INTERACTIONS

KW - FIBER MATRIX MODEL

KW - RESTRICTING JUNCTION

KW - INTERSTITIAL FLUID

KW - FUNCTIONAL-ASPECTS

KW - OLFACTORY SYSTEM

KW - BASIC CONCEPTS

KW - PERMEABILITY

KW - ULTRASTRUCTURE

U2 - 10.1002/glia.20642

DO - 10.1002/glia.20642

M3 - Article

SN - 0894-1491

VL - 56

SP - 699

EP - 708

JO - Glia

JF - Glia

IS - 7

ER -