Molecular Heterogeneity of the Brain Endothelium.
Molecular Heterogeneity of the Brain Endothelium.
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DOI：
10.3390/cimb45040227
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发表时间：
2023-04-16
影响因子：
3.1
通讯作者：
Harati, Rania
中科院分区：
文献类型：
--
作者：
Alnaqbi, Nada;Mohammad, Mohammad G.;Hamoudi, Rifat;Mabondzo, Aloise;Harati, Rania
关键词：
血脑屏障（BBB）是位于大脑微血管中的神经血管结构的一部分，它对维持大脑内稳态至关重要，但也阻止了大脑对大多数药物的吸收。由于其在神经药物治疗中的重要性，血脑屏障自100多年前被发现以来一直是广泛研究的主题。在了解屏障的结构和功能方面已经取得了重大进展。药物被重新设计以穿过血脑屏障。然而，尽管有这些努力，有效地克服血脑屏障以安全治疗脑部疾病仍然具有挑战性。大多数血脑屏障研究都将血脑屏障视为贯穿大脑不同区域的同质结构。然而，这种简化可能导致对血脑屏障功能的理解不足，并产生重大的治疗后果。从这个角度出发，我们分析了从大脑皮层和海马两个不同区域分离的小鼠大脑微血管中血脑屏障的基因和蛋白表达谱。分析内皮间连接蛋白（claudin-5）、3种ABC转运蛋白（p-糖蛋白、Bcrp和Mrp-1）和3种血脑屏障受体（lrp-1、TRF和GLUT-1）的表达谱。我们的基因和蛋白质分析表明，海马体中的脑内皮与大脑皮层的表达谱不同。具体而言，海马区的脑内皮细胞（BECs）表达abcb1、abcg2、lrp1和slc2a1基因水平高于皮质区BECs，且claudin-5呈上升趋势，而皮质区的BECs表达abcc1和trf基因水平高于海马区。在蛋白水平上，P-gp在海马中的表达明显高于皮层，而TRF在皮层中的表达则上调。这些数据表明血脑屏障的结构和功能并不均匀，这意味着药物在不同脑区之间的传递并不相似。因此，未来研究项目对血脑屏障异质性的认识对于有效的药物输送和脑部疾病的治疗至关重要。
The blood–brain barrier (BBB) is part of a neurovascular structure located in the brain’s micro vessels, that is essential to maintain brain homeostasis, but prevents the brain uptake of most drugs. Because of its importance in neuro-pharmacotherapy, the BBB has been the subject of extensive research since its discovery over 100 years ago. Major advances in understanding the structure and function of the barrier have been made. Drugs are re-designed to cross the BBB. However, despite these efforts, overcoming the BBB efficiently to treat brain diseases safely remains challenging. The majority of BBB research studies focus on the BBB as a homogenous structure throughout the different brain regions. However, this simplification may lead to an inadequate understanding of the BBB function with significant therapeutic consequences. From this perspective, we analyzed the gene and protein expression profiles of the BBB in the micro vessels from the brains of mice that were isolated from two different brain regions, namely the cortex and the hippocampus. The expression profile of the inter-endothelial junctional protein (claudin-5), three ABC transporters (P-glycoprotein, Bcrp and Mrp-1), and three BBB receptors (lrp-1, TRF and GLUT-1) were analyzed. Our gene and protein analysis showed that the brain endothelium in the hippocampus exhibits different expression profiles compared to the brain cortex. Specifically, brain endothelial cells (BECs) of the hippocampus express higher gene levels of abcb1, abcg2, lrp1, and slc2a1 compared to the BECs of the cortex regions with a trend of increase for claudin-5, while BECs of the cortex express higher gene levels of abcc1 and trf compared to the hippocampus. At the protein levels, the P-gp expression was found to be significantly higher in the hippocampus compared to the cortex, while TRF was found to be up-regulated in the cortex. These data suggest that the structure and function of the BBB are not homogeneous, and imply that drugs are not delivered similarly among the different brain regions. Appreciation of the BBB heterogeneity by future research programs is thus critical for efficient drug delivery and the treatment of brain diseases.
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影响因子：
7.2
作者：
Daneman, Richard;Prat, Alexandre
通讯作者：
Prat, Alexandre
影响因子：
6
作者：
Dallasta, LM;Pisarov, LA;Achim, CL
通讯作者：
Achim, CL
DOI：
10.1111/j.1749-6632.1988.tb51417.x
发表时间：
1988-01-01
影响因子：
5.2
作者：
Goldstein, G W
通讯作者：
Goldstein, G W
影响因子：
3
作者：
Baeten, Kim M.;Akassoglou, Katerina
通讯作者：
Akassoglou, Katerina
影响因子：
11.1
作者：
Ben-Zvi, A.;Liebner, S.
通讯作者：
Liebner, S.