The blood-brain barrier and glutamate
The blood-brain barrier and glutamate
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DOI：
10.3945/ajcn.2009.27462bb
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发表时间：
2009-09-01
影响因子：
7.1
通讯作者：
Hawkins, Richard A.
中科院分区：
文献类型：
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作者：
Hawkins, Richard A.
血浆中的谷氨酸浓度为50-100 μ mol/L;全脑中的谷氨酸浓度为10，000 - 12，000 μ mol/L，但细胞外液（ECFs）中的谷氨酸浓度仅为0.5-2 μ mol/L。低ECF浓度是最佳脑功能所必需的，由神经元、星形胶质细胞和血脑屏障（BBB）维持。脑毛细血管内皮细胞形成包围整个中枢神经系统的血脑屏障。紧密连接连接内皮细胞并将BBB分成腔域和腔外域。因此，进入或离开大脑的分子必须通过两层膜，每层膜都有不同的特性。促进载体仅存在于腔膜中，并且Na+依赖性谷氨酸协同转运体（兴奋性氨基酸转运体; EAAT）仅存在于近腔膜中。EAAT是二级转运蛋白，其偶联ECF和内皮细胞之间的Na+梯度以对抗现有的电化学梯度移动谷氨酸。因此，近腔膜中的EAAT将谷氨酸从ECF转移到内皮细胞，其中谷氨酸在易化载体上自由扩散到血液中。这种组织不允许净谷氨酸进入大脑;相反，它促进了谷氨酸的去除和ECF中低谷氨酸浓度的维持。这就解释了研究表明，BBB是不可渗透的谷氨酸，即使在高浓度下，除了在少数小区域有窗孔毛细血管（脑室周围器官）。最近，BBB在糖尿病中是否变得可渗透的问题已经出现。这个问题在饮食诱导的肥胖和胰岛素抵抗或链脲佐菌素诱导的糖尿病大鼠中进行了测试。这两种情况都没有对BBB谷氨酸转运产生任何可检测的影响。Am J Clin Nutr 2009; 90（增刊）：867 S-74 S。
Glutamate concentrations in plasma are 50-100 mu mol/L; in whole brain, they are 10,000-12,000 mu mol/L but only 0.5-2 mu mol/L in extracellular fluids (ECFs). The low ECF concentrations, which are essential for optimal brain function, are maintained by neurons, astrocytes, and the blood-brain barrier (BBB). Cerebral capillary endothelial cells form the BBB that surrounds the entire central nervous system. Tight junctions connect endothelial cells and separate the BBB into luminal and abluminal domains. Molecules entering or leaving the brain thus must pass 2 membranes, and each membrane has distinct properties. Facilitative carriers exist only in luminal membranes, and Na+-dependent glutamate cotransporters ( excitatory amino acid transporters; EAATs) exist exclusively in abluminal membranes. The EAATs are secondary transporters that couple the Na+ gradient between the ECF and the endothelial cell to move glutamate against the existing electrochemical gradient. Thus, the EAATs in the abluminal membrane shift glutamate from the ECF to the endothelial cell where glutamate is free to diffuse into blood on facilitative carriers. This organization does not allow net glutamate entry to the brain; rather, it promotes the removal of glutamate and the maintenance of low glutamate concentrations in the ECF. This explains studies that show that the BBB is impermeable to glutamate, even at high concentrations, except in a few small areas that have fenestrated capillaries (circumventricular organs). Recently, the question of whether the BBB becomes permeable in diabetes has arisen. This issue was tested in rats with diet-induced obesity and insulin resistance or with streptozotocin-induced diabetes. Neither condition produced any detectable effect on BBB glutamate transport. Am J Clin Nutr 2009; 90(suppl):867S-74S.