Abstract:
Red blood cells circulating through the brain are briefly but closely apposed to the capillary endothelium. We hypothesized that this contact provides a nearly direct pathway for metabolic substrate transfer to neural cells that complements the better characterized plasma to endothelium transfer. While brain function is considered independent of normal fluctuations in blood glucose concentration, this is not borne out by persons with glucose transporter I (GLUT1) deficiency (G1D). In them, encephalopathy is often ameliorated by meal or carbohydrate administration, and this enabled us to test our hypothesis: Since red blood cells contain glucose, and since the red cells of G1D individuals are also deficient in GLUT1, replacing them with normal donor cells via exchange transfusion could augment erythrocyte to neural cell glucose transport via mass action in the setting of unaltered erythrocyte count or plasma glucose abundance. This motivated us to perform red blood cell exchange in 3 G1D persons. There were rapid, favorable and unprecedented changes in cognitive, electroencephalographic and quality-of-life measures. The hypothesized transfer mechanism was further substantiated by in vitro measurement of direct erythrocyte to endothelial cell glucose flux. The results also indicate that the adult intellect is capable of significant enhancement without deliberate practice. ClinicalTrials.gov registration: NCT04137692 https://clinicaltrials.gov/ct2/show/NCT04137692.
摘要:
通过大脑循环的红细胞短暂但紧密地与毛细血管内皮并列。我们假设这种接触为代谢底物转移到神经细胞提供了几乎直接的途径,从而补充了更好表征的血浆到内皮的转移。虽然脑功能被认为与血糖浓度的正常波动无关,葡萄糖转运蛋白I(GLUT1)缺乏症(G1D)的患者并未证实这一点。在他们身上,脑病通常通过膳食或碳水化合物管理来改善,这使我们能够检验我们的假设:由于红细胞含有葡萄糖,并且由于G1D个体的红细胞也缺乏GLUT1,因此在红细胞计数或血浆葡萄糖丰度未改变的情况下,通过交换输血将其替换为正常的供体细胞,可以通过质量作用来增加红细胞向神经细胞的葡萄糖转运。这促使我们在3个G1D人中进行红细胞交换。有快速的,认知的有利和前所未有的变化,脑电图和生活质量测量。通过体外测量直接红细胞到内皮细胞的葡萄糖通量进一步证实了假设的转移机制。结果还表明,无需刻意练习,成人的智力就能够显着增强。ClinicalTrials.gov注册:NCT04137692https://clinicaltrials.gov/ct2/show/NCT04137692。