The ontogeny of P-glycoprotein in the developing human blood–brain barrier: implication for opioid toxicity in neonates
2015; Springer Nature; Volume: 78; Issue: 4 Linguagem: Inglês
10.1038/pr.2015.119
ISSN1530-0447
AutoresJessica Lam, Stephanie Baello, Majid Iqbal, Lauren E. Kelly, Patrick Shannon, David Chitayat, Stephen G. Matthews, Gideon Koren,
Tópico(s)Neonatal Health and Biochemistry
ResumoNeonates have been shown to have a heightened sensitivity to the central depressive effects of opioids compared to older infants and adults. The limited development of P-glycoprotein (P-gp) may limit the ability of the neonate to efflux morphine from the brain back to the systemic circulation. The objective of the study was to determine the ontogeny of P-gp in the human brain. Postmortem cortex samples from gestational age (GA) 20–26 wk, GA 36–40 wk, postnatal age (PNA) 0–3 mo, PNA 3–6 mo, and adults were immunostained for P-gp. The intensity of P-gp staining in adults was significantly higher compared to at GA 20–26 wk (P < 0.05), GA 36–40 wk (P < 0.05), and PNA 0–3 mo (P < 0.05). P-gp intensity at GA 20–26 wk (P < 0.05), GA 36–40 wk (P < 0.05), and PNA 0–3 mo (P < 0.05) was significantly lower compared to at PNA 3–6 mo. P-gp expression in the brain is limited at birth, increases with postnatal maturation, and reaches adult levels at ~3–6 mo of age. Given the immaturity of blood–brain barrier (BBB) P-gp after birth, morphine may concentrate in the brain. This provides mechanistic support to life threatening opioid toxicity seen with maternal codeine use during breastfeeding.
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