Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain

TY - JOUR

T1 - Physiology and molecular biology of barrier mechanisms in the fetal and neonatal brain

AU - Saunders, Norman R.

AU - Dziegielewska, Katarzyna M.

AU - Møllgård, Kjeld

AU - Habgood, Mark D.

PY - 2018

Y1 - 2018

N2 - Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the ‘blood–brain barrier’. These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products, and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood–brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting.

AB - Properties of the local internal environment of the adult brain are tightly controlled providing a stable milieu essential for its normal function. The mechanisms involved in this complex control are structural, molecular and physiological (influx and efflux transporters) frequently referred to as the ‘blood–brain barrier’. These mechanisms include regulation of ion levels in brain interstitial fluid essential for normal neuronal function, supply of nutrients, removal of metabolic products, and prevention of entry or elimination of toxic agents. A key feature is cerebrospinal fluid secretion and turnover. This is much less during development, allowing greater accumulation of permeating molecules. The overall effect of these mechanisms is to tightly control the exchange of molecules into and out of the brain. This review presents experimental evidence currently available on the status of these mechanisms in developing brain. It has been frequently stated for over nearly a century that the blood–brain barrier is not present or at least is functionally deficient in the embryo, fetus and newborn. We suggest the alternative hypothesis that the barrier mechanisms in developing brain are likely to be appropriately matched to each stage of its development. The contributions of different barrier mechanisms, such as changes in constituents of cerebrospinal fluid in relation to specific features of brain development, for example neurogenesis, are only beginning to be studied. The evidence on this previously neglected aspect of brain barrier function is outlined. We also suggest future directions this field could follow with special emphasis on potential applications in a clinical setting.

KW - amino acids

KW - blood vessels

KW - blood-brain barrier

KW - cerebrospinal fluid

KW - choroid plexus

KW - electrolytes

KW - electron microscope

KW - embryo

KW - endothelium

KW - epithelium

KW - gene transcripts

KW - immunohistochemistry

KW - ion gradients

KW - meninges

KW - protein

KW - tight junctions

KW - transport

U2 - 10.1113/JP275376

DO - 10.1113/JP275376

M3 - Review

C2 - 29774535

AN - SCOPUS:85050503031

SN - 0022-3751

VL - 596

SP - 5723

EP - 5756

JO - The Journal of Physiology

JF - The Journal of Physiology

IS - 23

ER -