When drugs exert their effects in the brain, linear extrapolation of doses from adults could be harmful for children as the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB) function is still immature. More specifically, age-related variation in membrane transporters may impact brain disposition. As human data on brain transporter expression is scarce, age dependent [gestational age (GA), postnatal age (PNA), and postmenstrual age (PMA)] variation in immunohistochemical localization and staining intensity of the ABC transporters P-glycoprotein (Pgp), breast cancer resistance protein (BCRP), and multidrug resistance-associated proteins 1, 2, 4, and 5 (MRP1/2/4/5) was investigated. Post mortem brain cortical and ventricular tissue was derived from 23 fetuses (GA range 12.9-39 weeks), 17 neonates (GA range 24.6-41.3 weeks, PNA range 0.004-3.5 weeks), 8 children (PNA range 0.1-3 years), and 4 adults who died from a wide variety of underlying conditions. In brain cortical BBB, immunostaining increased with age for Pgp and BCRP, while in contrast, MRP1 and MRP2 staining intensity appeared higher in fetuses, neonates, and children, as compared to adults. BCSFB was positively stained for Pgp, MRP1, and MRP2 and appeared stable across age, while BCRP was not detected. MRP4 and MRP5 were not detected in BBB or BCSFB. In conclusion, human BBB and BCSFB ABC membrane transporters show brain location and transporter-specific maturation.

中文翻译：

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人血脑屏障和血脑脊液屏障ABC药物转运蛋白表达的发育模式。

当药物在大脑中发挥作用时，成人的线性外推剂量可能对儿童有害，因为血脑屏障（BBB）和血液CSF屏障（BCSFB）功能仍不成熟。更具体地说，膜转运蛋白中与年龄相关的变化可能会影响大脑的处置。由于关于脑转运蛋白表达的人类数据稀少，ABC转运蛋白P-糖蛋白（Pgp）的免疫组织化学定位和染色强度依赖于年龄[胎龄（GA），出生后年龄（PNA）和月经后（PMA）]，研究了乳腺癌抗性蛋白（BCRP）和多药耐药性相关蛋白1、2、4和5（MRP1 / 2/4/5）。验尸后大脑皮层和心室组织来自23胎（GA范围12.9-39周），17例新生儿（GA范围24.6-41.3周，PNA范围0.004-3）。5周），8名儿童（PNA范围为0.1-3岁）和4名因多种潜在疾病死亡的成年人。在大脑皮层血脑屏障中，Pgp和BCRP的免疫染色随着年龄的增长而增加，与此相反，与成年人相比，胎儿，新生儿和儿童的MRP1和MRP2染色强度更高。BCSFB的Pgp，MRP1和MRP2染色呈阳性，并且在整个年龄段均表现稳定，而未检测到BCRP。在BBB或BCSFB中未检测到MRP4和MRP5。总之，人类BBB和BCSFB ABC膜转运蛋白表现出大脑定位和转运蛋白特异性成熟。新生儿和儿童，与成人相比。BCSFB的Pgp，MRP1和MRP2染色呈阳性，并且在整个年龄段均表现稳定，而未检测到BCRP。在BBB或BCSFB中未检测到MRP4和MRP5。总之，人类BBB和BCSFB ABC膜转运蛋白表现出大脑定位和转运蛋白特异性成熟。新生儿和儿童，与成人相比。BCSFB的Pgp，MRP1和MRP2染色呈阳性，并且在整个年龄段均表现稳定，而未检测到BCRP。在BBB或BCSFB中未检测到MRP4和MRP5。总之，人类BBB和BCSFB ABC膜转运蛋白表现出大脑定位和转运蛋白特异性成熟。