Red blood cells as glucose carriers to the human brain: Modulation of cerebral activity by erythrocyte exchange transfusion in Glut1 deficiency (G1D)

Richard C. Wang, Eunice E. Lee, Nicole De Simone, Gauri Kathote, Sharon Primeaux, Adrian Avila, Dong Min Yu, Mark Johnson, Levi B. Good, Vikram Jakkamsetti, Ravi Sarode, Alice Ann Holland, Juan M. Pascual

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)357-368
Number of pages12
JournalJournal of Cerebral Blood Flow and Metabolism
Volume43
Issue number3
DOIs
StatePublished - Mar 2023

Keywords

  • Glucose
  • electroencephalography
  • erythrocyte
  • exchange transfusion
  • flux

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology
  • Cardiology and Cardiovascular Medicine

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