Abstract
The need to protect neural tissue from toxins or other substances is as old as neural tissue itself. Early recognition of this need has led to more than a century of investigation of the blood-brain barrier (BBB). Many aspects of this important neuroprotective barrier have now been well established, including its cellular architecture and barrier and transport functions. Unsurprisingly, most research has had a human orientation, using mammalian and other animal models to develop translational research findings. However, cell layers forming a barrier between vascular spaces and neural tissues are found broadly throughout the invertebrates as well as in all vertebrates. Unfortunately, previous scenarios for the evolution of the BBB typically adopt a classic, now discredited ‘scala naturae’ approach, which inaccurately describes a putative evolutionary progression of the mammalian BBB from simple invertebrates to mammals. In fact, BBB-like structures have evolved independently numerous times, complicating simplistic views of the evolution of the BBB as a linear process. Here, we review BBBs in their various forms in both invertebrates and vertebrates, with an emphasis on the function, evolution, and conditional relevance of popular animal models such as the fruit fly and the zebrafish to mammalian BBB research.
Highlights
We note the irony of our taxonomic approach and emphasize again that the BBB independently evolved numerous times, and so the order of which we discuss the various taxa does not imply an evolutionary progression of the blood-brain barrier
In isolated brain capillaries of rats exposed to tetrachlorodibenzo-p-dioxin (TCDD), there is significantly increased activity and expression of P-glycoprotein [84], while brain capillaries of mice exposed to polychlorinated biphenyls (PCBs) have deranged expression of tight junction proteins associated with increased BBB permeability [85]
In the garter snake Thamnophis sirtalis, which may feed on highly toxic Taricha newts producing tetrodatoxin (TTX), the neurons of the central nervous system (CNS) show no particular resistance to TTX, suggesting active BBB exclusion of this toxin from the neural tissue [135]
Summary
The current textbook definition of the blood-brain barrier (BBB) typically reads something such as: “a physical barrier made of endothelial cells that line capillaries of the brain; it provides a semi-permeable barrier movement of certain substances into and out of the brain to maintain homeostasis of the central nervous system” This description of the BBB is generally accurate, there are important caveats and nuances of the BBB that are not captured by this definition. This definition is species-agnostic, but the implication is that the description of ‘the BBB’ is for a mammal, or a human This definition provides little information with respect to how the BBB evolved to become what it is today across taxa. We discuss the need for an ecological and evolutionary framework and indicate new directions for future experiments in the field
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