Glutamate Efflux at the Blood-Brain Barrier: Cellular Mechanisms and Potential Clinical Relevance

TY - JOUR

T1 - Glutamate Efflux at the Blood-Brain Barrier

T2 - Cellular Mechanisms and Potential Clinical Relevance

AU - Cederberg-Helms, Hans Christian

AU - Uhd-Nielsen, Carsten

AU - Brodin, Birger

N1 - Copyright © 2014 IMSS. Published by Elsevier Inc. All rights reserved.

PY - 2014/11/1

Y1 - 2014/11/1

N2 - L-Glutamate is considered the most important excitatory amino acid in the mammalian brain. Strict control of its concentration in the brain interstitial fluid is important to maintain neurotransmission and avoid excitotoxicity. The role of astrocytes in handling L-glutamate transport and metabolism is well known, however endothelial cells may also play an important role through mediating brain-to-blood L-glutamate efflux. Expression of excitatory amino acid transporters has been demonstrated in brain endothelial cells of bovine, human, murine, rat and porcine origin. These can account for high affinity concentrative uptake of L-glutamate from the brain interstitial fluid into the capillary endothelial cells. The mechanisms in between L-glutamate uptake in the endothelial cells and L-glutamate appearing in the blood are still unclear and may involve a luminal transporter for L-glutamate, metabolism of L-glutamate and transport of metabolites or a combination of the two. However, both invitro and invivo studies demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. This review summarizes the current knowledge on the brain-to-blood L-glutamate efflux hypothesis including possible mechanisms to account for the transport, invivo studies on blood glutamate scavenging and potential clinical relevance of the phenomenon.

AB - L-Glutamate is considered the most important excitatory amino acid in the mammalian brain. Strict control of its concentration in the brain interstitial fluid is important to maintain neurotransmission and avoid excitotoxicity. The role of astrocytes in handling L-glutamate transport and metabolism is well known, however endothelial cells may also play an important role through mediating brain-to-blood L-glutamate efflux. Expression of excitatory amino acid transporters has been demonstrated in brain endothelial cells of bovine, human, murine, rat and porcine origin. These can account for high affinity concentrative uptake of L-glutamate from the brain interstitial fluid into the capillary endothelial cells. The mechanisms in between L-glutamate uptake in the endothelial cells and L-glutamate appearing in the blood are still unclear and may involve a luminal transporter for L-glutamate, metabolism of L-glutamate and transport of metabolites or a combination of the two. However, both invitro and invivo studies demonstrated blood-to-brain transport of L-glutamate, at least during pathological events. This review summarizes the current knowledge on the brain-to-blood L-glutamate efflux hypothesis including possible mechanisms to account for the transport, invivo studies on blood glutamate scavenging and potential clinical relevance of the phenomenon.

U2 - 10.1016/j.arcmed.2014.11.004

DO - 10.1016/j.arcmed.2014.11.004

M3 - Journal article

C2 - 25446623

SN - 0188-4409

VL - 45

SP - 639

EP - 645

JO - Archives of Medical Research

JF - Archives of Medical Research

IS - 8

ER -