Glut1 glucose transporter activity in human brain injury
Glut1 glucose transporter activity in human brain injury
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DOI：
10.1089/neu.1996.13.523
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发表时间：
1996-09-01
影响因子：
4.2
通讯作者：
Caron, MJ
中科院分区：
文献类型：
--
作者：
Cornford, EM;Hyman, S;Caron, MJ
血脑屏障 (BBB) 上的主要葡萄糖转运蛋白是 Glut1 同工型，转运蛋白密度被认为是脑代谢率的指标。在本研究中，研究了 2 名患者急性创伤性脑损伤后 7-8 小时切除的组织中葡萄糖转运蛋白的表达。光学显微镜免疫化学显示，在靠近小血管损伤部位的微血管内皮细胞中，有一个 Glut1 葡萄糖转运蛋白亚型完全丧失的区域，同心地被可变 Glut1 的狭窄区域包围，远端被毛细血管包围，在未破坏的实质中具有典型的免疫反应性内皮细胞。反应性不同的毛细血管显示出交替出现的 Glut1 密度大幅降低和高反应性的区域，表明邻近内皮细胞中转运蛋白活性的密度较高和较低。定量电子显微镜免疫金分析表明，转运蛋白主要定位于管腔和近腔内皮膜，在细胞质中的反应性较低；周细胞 Glut1 略高于背景水平。在 Glut1 转运蛋白免疫反应性降低的内皮部分中，Glut1 表位的管腔：管腔比值小于 1；而它大于高反应性内皮细胞的统一。每微米毛细血管膜的 Glut1 免疫反应位点数量与之前报道的癫痫切除中的 Glut1 密度没有显着差异，并且比人类红细胞高约 2 至 3 倍。在相同的组织样本中，人血清白蛋白的定性免疫金电子显微镜显示该蛋白质（MW 65,000）从血管间隙渗漏到毛细血管周围区域。因此，在急性损伤的大脑毛细血管中观察到的高 Glut1 密度与屏障功能受损同时发生。
The principal glucose transporter at the blood-brain barrier (BBB) is the Glut1 isoform, and transporter density is believed to be an index of cerebral metabolic rate. In the present study, glucose transporter expression was studied in tissue resected 7-8 h after acute traumatic brain injuries in 2 patients. Light microscopic immunochemistry indicated a zone of complete loss of the Glut1 glucose transporter isoform in microvessel endothelial cells adjacent to sites of small vessel injury, concentrically surrounded by a narrow zone of variable Glut1, and distally surrounded by capillaries with typically immunoreactive endothelia in nondisrupted parenchyma. Variably reactive capillaries displayed alternating sectors of greatly reduced and highly reactive Glut1 density, suggesting a high density and low density of transporter activity in contiguous endothelial cells. Quantitative electron microscopic immunogold analyses demonstrated that the transporter was predominantly localized to the luminal and abluminal endothelial membranes, with lesser reactivity in cytoplasm; pericyte Glut1 was minimally above background levels. In endothelial sectors with reduced Glut1 transporter immunoreactivity, the luminal:abluminal ratio of Glut1 epitopes was less than unity; while it is greater than unity in highly reactive endothelial cells. The number of Glut1-immunoreactive sites per micrometer of capillary membrane was not signficantly different from previous reported Glut1 density in seizure resections, and about 2- to 3-fold higher than in human red cells. In the same tissue samples, qualitative immunogold electron microscopy of human serum albumin indicated leakage of this protein (MW 65,000) from the vascular space into pericapillary regions. Thus the high Glut1 density observed in capillaries from acutely injured brain occurs concomitantly with compromised barrier function.