Research Topic

Ontogeny and Phylogeny of Brain Barrier Mechanisms

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The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these interfaces are across cerebral blood vessels (blood-brain barrier) choroid plexuses ...

The brain functions within an internal environment that is determined and controlled by morphological structures and cellular mechanisms present at interfaces between the brain and the rest of the body. In vertebrates these interfaces are across cerebral blood vessels (blood-brain barrier) choroid plexuses (blood-cerebrospinal fluid barrier) and pia-arachnoid. There is a CSF-brain barrier in the neuroepithelium lining the ventricular system that is only present in embryos. There is now substantial evidence that many of the brain barrier mechanisms develop early and that in some cases they are functionally more active and even specialized compared to adult barriers. Therefore barriers in developing brain should be viewed as adapted appropriately for the growing brain and not, as is still widely believed, immature.

Considerable advances in our understanding of these barrier mechanisms have come from studies of the developing brain and invertebrates. A striking aspect, to be highlighted in this special edition, is that many of the molecular mechanisms in these very diverse species are similar despite differences in the cellular composition of the interfaces.

The Frontiers series will comprise articles in three sections: Original studies, Reviews and Myths & Misconceptions. Original articles would provide new information on molecular and cellular mechanisms in primate (Ek, Virgintino) and rodent barriers (Daneman, Dziegielewska, Liddelow). Molecular modeling is a new approach to understanding transport across brain barriers illustrated by the first model of a protein transport mechanism in developing choroid plexus (Kuiper). The Reviews section would include evolutionary perspectives of the blood-brain and blood-CSF barriers (Abbott and Korzh). There would also be detailed reviews of the current state of understanding of different interfaces and their functional mechanisms in developing brain (Bauer, Watts, Daneman, Eliceiri, Gjersi-Egea, Liddelow, Richardson, Virgintino, Taylor, Møllgård) and in invertebrates (Bainton, Klambt). These would be pulled together by comparisons of blood-brain barrier and blood-CSF barriers (Daneman) and an interspecies comparison of brain barriers (Bainton). Different aspects of the relationship between properties of the internal environment of the brain and its development would be discussed. (Molnar, Johansson). A neglected area, namely non-barrier regions in the developing brain would also be covered (Møllgård). A clinical perspective on barrier disruption in neonatal stroke would be provided (Vexler).

Progress in this field is hampered by many prevailing myths about barrier function, combined with methodologies that are not always appropriately selected or interpreted. These would be covered in the Misconceptions & Myths section, including historical aspects (Saunders) discussion of the paracellular pathway, a central dogma of epithelial and endothelial biology (Saunders) and a review of markers used to define brain barrier integrity in development and in pathological conditions (Habgood). Use of inappropriate markers has caused considerable confusion and unreliable interpretation in many published studies. There are major problems associated with attempts to obtain antibody entry into the brain that merit separate discussion (Watts). A final summary with contributions from all authors would be edited by Stolp. This would define the main unanswered but answerable questions in the field and what the impediments to progress may be.


Important Note: All contributions to this Research Topic must be within the scope of the section and journal to which they are submitted, as defined in their mission statements. Frontiers reserves the right to guide an out-of-scope manuscript to a more suitable section or journal at any stage of peer review.

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