Efflux transporters in blood-brain interfaces of the developing brain.
Efflux transporters in blood-brain interfaces of the developing brain.
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DOI：
10.3389/fnins.2015.00021
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发表时间：
2015
影响因子：
4.3
通讯作者：
Ghersi-Egea JF
中科院分区：
文献类型：
--
作者：
Strazielle N;Ghersi-Egea JF
形成血脑屏障（BBB）的脑微血管内皮和形成血脑脊液屏障（BCSFB）的脉络丛上皮充当中枢神经系统的守门人。脆弱的发育中的大脑暴露于化学损伤可能会对大脑成熟产生严重后果，并导致终生神经系统疾病。因此，血脑界面有效保护未成熟大脑的能力是一个重要的病理生理学问题。这也是我们了解药物进入新生儿和儿科患者大脑的关键。在发育早期，穿过屏障的非特异性细胞旁扩散受到限制，但这些界面的其他神经保护特性在发育中的大脑和成年大脑之间有所不同。本综述重点关注各类外排转运蛋白的发育表达和功能。这些包括 ATP 结合盒转运蛋白家族 ABCB、ABCC、ABCG 的多特异性转运蛋白，溶质载体家族 SLC21/SLCO 和 SLC22 的有机阴离子和阳离子转运蛋白，以及 SLC15 家族的肽转运蛋白。这些转运蛋白在阻止药物、环境毒物和内源性代谢物等血源性分子进入大脑方面发挥着关键作用，或者在增加大脑中潜在有害有机离子的清除方面发挥着关键作用。可用于实验动物和人类的有限数据强调了转运蛋白特异性表达和功能的发育模式，这在血脑界面之间是不同的。 BCSFB 比 BBB 更早达到成体表型。 BBB 的外排转运蛋白似乎受到神经祖细胞和星形胶质细胞在发育过程中随后分泌的各种因子的调节。它们的表达还受到氧化应激、炎症和接触外源性诱导剂的调节。更好地了解发育过程中的这些调节途径，特别是氧化应激和异生素触发的信号传导途径，可能会为治疗操作开辟新的机会，以改善或恢复围产期损伤情况下血脑界面的神经保护功能。
The cerebral microvessel endothelium forming the blood-brain barrier (BBB) and the epithelium of the choroid plexuses forming the blood-CSF barrier (BCSFB) operate as gatekeepers for the central nervous system. Exposure of the vulnerable developing brain to chemical insults can have dramatic consequences for brain maturation and lead to life-long neurological diseases. The ability of blood-brain interfaces to efficiently protect the immature brain is therefore an important pathophysiological issue. This is also key to our understanding of drug entry into the brain of neonatal and pediatric patients. Non-specific paracellular diffusion through barriers is restricted early during development, but other neuroprotective properties of these interfaces differ between the developing and adult brains. This review focuses on the developmental expression and function of various classes of efflux transporters. These include the multispecific transporters of the ATP-binding cassette transporter families ABCB, ABCC, ABCG, the organic anion and cation transporters of the solute carrier families SLC21/SLCO and SLC22, and the peptide transporters of the SLC15 family. These transporters play a key role in preventing brain entry of blood-borne molecules such as drugs, environmental toxicants, and endogenous metabolites, or else in increasing the clearance of potentially harmful organic ions from the brain. The limited data available for laboratory animals and human highlight transporter-specific developmental patterns of expression and function, which differ between blood-brain interfaces. The BCSFB achieves an adult phenotype earlier than BBB. Efflux transporters at the BBB appear to be regulated by various factors subsequently secreted by neural progenitors and astrocytes during development. Their expression is also modulated by oxidative stress, inflammation, and exposure to xenobiotic inducers. A better understanding of these regulatory pathways during development, in particular the signaling pathways triggered by oxidative stress and xenobiotics, may open new opportunities to therapeutic manipulation in view to improve or restore neuroprotective functions of the blood-brain interfaces in the context of perinatal injuries.
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影响因子：
3.7
作者：
Gazzin S;Berengeno AL;Strazielle N;Fazzari F;Raseni A;Ostrow JD;Wennberg R;Ghersi-Egea JF;Tiribelli C
通讯作者：
Tiribelli C
影响因子：
3.7
作者：
Fenart, L;Buée-Scherrer, V;Dehouck, MP
通讯作者：
Dehouck, MP
影响因子：
4.2
作者：
D'Angelo, Barbara;Ek, C. Joakim;Mallard, Carina
通讯作者：
Mallard, Carina
影响因子：
4.8
作者：
Baello, Stephanie;Iqbal, Majid;Matthews, Stephen G.
通讯作者：
Matthews, Stephen G.
影响因子：
2.5
作者：
CALEY, DW;MAXWELL, DS
通讯作者：
MAXWELL, DS