Glutamate Transporters in the Blood-Brain Barrier

Hans Christian Cederberg Helms, Carsten Uhd Nielsen, Helle S Waagepetersen, Birger Brodin

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Abstract

The amino acid L-glutamate serves a number of roles in the central nervous system, being an excitatory neurotransmitter, metabolite, and building block in protein synthesis. During pathophysiological events, where L-glutamate homeostasis cannot be maintained, the increased brain interstitial fluid concentration of L-glutamate causes excitotoxicity. A tight control of the brain interstitial fluid L-glutamate levels is therefore imperative, in order to maintain optimal neurotransmission and to avoid such excitotoxicity. The blood-brain barrier, i.e., the endothelial lining of the brain capillaries, regulates the exchange of nutrients, gases, and metabolic waste products between plasma and brain interstitial fluid. It has been suggested that brain capillary endothelial cells could play an important role in L-glutamate homeostasis by mediating brain-to-blood L-glutamate efflux. Both in vitro and in vivo studies have demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. A number of studies have shown that brain endothelial cells express excitatory amino acid transporters, which may account for abluminal concentrative uptake of L-glutamate into the capillary endothelial cells. The mechanisms underlying transendothelial L-glutamate transport are however still not well understood. The present chapter summarizes the current knowledge on blood-brain barrier L-glutamate transporters and the suggested pathways for the brain-to-blood L-glutamate efflux.

Original languageEnglish
Title of host publicationGlial Amino Acid Transporters
EditorsArturo Ortega, Arme Schousboe
PublisherSpringer
Publication date23. Jul 2017
Edition1
Pages297-314
Chapter15
ISBN (Print)978-3-319-55767-0
ISBN (Electronic)978-3-319-55769-4
DOIs
Publication statusPublished - 23. Jul 2017
SeriesAdvances in Neurobiology
Number1
Volume16
ISSN2190-5215

Keywords

  • Brain glutamate efflux
  • EAAT
  • Excitotoxicity
  • Glutamate metabolism
  • Neurovascular unit
  • Animals
  • Glutamic Acid/metabolism
  • Humans
  • Biological Transport/physiology
  • Blood-Brain Barrier/metabolism
  • Amino Acid Transport System X-AG/metabolism

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