Recent developments in understanding barrier mechanisms in the developing brain: Drugs and drug transporters in pregnancy, susceptibility or protection in the fetal brain?

TY - JOUR

T1 - Recent developments in understanding barrier mechanisms in the developing brain

T2 - Drugs and drug transporters in pregnancy, susceptibility or protection in the fetal brain?

AU - Saunders, Norman R.

AU - Dziegielewska, Katarzyna M.

AU - Møllga°rd, Kjeld

AU - Habgood, Mark D.

PY - 2019

Y1 - 2019

N2 - Efflux mechanisms situated in various brain barrier interfaces control drug entry into the adult brain; this review considers the effectiveness of these protective mechanisms in the embryo, fetus, and newborn brain. The longstanding belief that the blood-brain barrier is absent or immature in the fetus and newborn has led to many misleading statements with potential clinical implications. The immature brain is undoubtedly more vulnerable to damage by drugs and toxins; as is reviewed here, some developmentally regulated normal brain barrier mechanisms probably contribute to this vulnerability. We propose that the functional status of brain barrier efflux mechanisms should be investigated at different stages of brain development to provide a rational basis for the use of drugs in pregnancy and in newborns, especially in those prematurely born, where protection usually provided by the placenta is no longer present.

AB - Efflux mechanisms situated in various brain barrier interfaces control drug entry into the adult brain; this review considers the effectiveness of these protective mechanisms in the embryo, fetus, and newborn brain. The longstanding belief that the blood-brain barrier is absent or immature in the fetus and newborn has led to many misleading statements with potential clinical implications. The immature brain is undoubtedly more vulnerable to damage by drugs and toxins; as is reviewed here, some developmentally regulated normal brain barrier mechanisms probably contribute to this vulnerability. We propose that the functional status of brain barrier efflux mechanisms should be investigated at different stages of brain development to provide a rational basis for the use of drugs in pregnancy and in newborns, especially in those prematurely born, where protection usually provided by the placenta is no longer present.

KW - Blood-brain barrier

KW - Cerebrospinal fluid

KW - Choroid plexus

KW - Efflux transporters

U2 - 10.1146/annurev-pharmtox-010818-021430

DO - 10.1146/annurev-pharmtox-010818-021430

M3 - Review

C2 - 30183506

AN - SCOPUS:85059799068

SN - 0362-1642

VL - 59

SP - 487

EP - 505

JO - Annual Review of Pharmacology and Toxicology

JF - Annual Review of Pharmacology and Toxicology

ER -