TY - CHAP

T1 - Glutamate Transporters in the Blood-Brain Barrier

AU - Helms, Hans Christian Cederberg

AU - Nielsen, Carsten Uhd

AU - Waagepetersen, Helle Sønderby

AU - Brodin, Birger

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1007/978-3-319-55769-4_15

DO - 10.1007/978-3-319-55769-4_15

M3 - Book chapter

C2 - 28828617

VL - 16

T3 - Advances in Neurobiology

SP - 297

EP - 314

BT - Glial Amino Acid Transporters

ER -