@article{c9b8a143f5ad4953beb11570d558087e,
title = "Homeostasis of glutamate in brain fluids: An accelerated brain-to-blood efflux of excess glutamate is produced by blood glutamate scavenging and offers protection from neuropathologies",
abstract = "l-Glutamate (Glu) homeostasis in brain extracellular fluids and its maintenance at low micromolar concentrations in the face of the extremely high Glu concentrations present in brain cells and synaptic vesicles have been commonly attributed to the very effective action of glutamate transporters present on neuronal and glial cells. This view however does not take into account the fact that the brain is highly vascularized and that the vasculature harbors a high density of glutamate transporters. In this article, we review the accumulated data establishing the existence of an efflux of excess Glu from brain extracellular fluids into blood. We describe plausible mechanisms accounting for this efflux and present evidence that the brain-to-blood Glu efflux is modulated by blood Glu levels and can be accelerated by blood Glu scavenging. The latter procedure shown here to afford brain neuroprotection in a rat model of closed head injury could be applicable, as a first-line therapy, in the various acute brain insults characterized by excess Glu in brain fluids.",
keywords = "capillary endothelial cells, closed head injury, dual-probe microdialysis, glutamate transporters, neuroprotection",
author = "Teichberg, {V. I.} and K. Cohen-Kashi-Malina and I. Cooper and A. Zlotnik",
note = "Funding Information: We are extremely thankful to Prof. J. Storm-Mathisen for his critical reading of our manuscript and for suggesting that the Gln–glutamate cycle could fully account for our data. Our work was supported in part by grants to V.I.T. from the Nella and Leon Benoziyo Center for Neurological Diseases; the Irwin Green Fund for Studying the Development of the Brain, the Carl and Micaela Einhorn-Dominic Institute for Brain Research, the Weizmann-Negri Fund and the Yeshaya Horowitz Foundation. V.I.T. is the incumbent of the Louis and Florence Katz-Cohen Chair of Neuropharmacology. The authors wish to state that all animal experiments described in this paper were conducted according to the recommendations of the Declarations of Helsinki and Tokyo, and to the Guidelines for the Use of Experimental Animals of the European Community and were approved by the Animal Care Committees of the Weizmann Institute of Science and Ben-Gurion University of the Negev. All efforts were made to reduce to a minimum the number of animals used in this study and minimize their suffering.",
year = "2009",
month = jan,
day = "12",
doi = "10.1016/j.neuroscience.2008.02.075",
language = "English",
volume = "158",
pages = "301--308",
journal = "Neuroscience",
issn = "0306-4522",
publisher = "Elsevier Ltd.",
number = "1",
}