The blood-brain barrier and glutamate

Abstract

Glutamate concentrations in plasma are 50-100 micromol/L; in whole brain, they are 10,000-12,000 micromol/L but only 0.5-2 micromol/L in extracellular fluids (ECFs). The low ECF concentrations, which are essential for optimal brain function, are maintained by neurons, astrocytes, and the blood-brain barrier (BBB). Cerebral capillary endothelial cells form the BBB that surrounds the entire central nervous system. Tight junctions connect endothelial cells and separate the BBB into luminal and abluminal domains. Molecules entering or leaving the brain thus must pass 2 membranes, and each membrane has distinct properties. Facilitative carriers exist only in luminal membranes, and Na(+)-dependent glutamate cotransporters (excitatory amino acid transporters; EAATs) exist exclusively in abluminal membranes. The EAATs are secondary transporters that couple the Na(+) gradient between the ECF and the endothelial cell to move glutamate against the existing electrochemical gradient. Thus, the EAATs in the abluminal membrane shift glutamate from the ECF to the endothelial cell where glutamate is free to diffuse into blood on facilitative carriers. This organization does not allow net glutamate entry to the brain; rather, it promotes the removal of glutamate and the maintenance of low glutamate concentrations in the ECF. This explains studies that show that the BBB is impermeable to glutamate, even at high concentrations, except in a few small areas that have fenestrated capillaries (circumventricular organs). Recently, the question of whether the BBB becomes permeable in diabetes has arisen. This issue was tested in rats with diet-induced obesity and insulin resistance or with streptozotocin-induced diabetes. Neither condition produced any detectable effect on BBB glutamate transport.

The Efficiency of Glutamate Uptake Differs between Neonatal and Adult Cortical Microvascular Endothelial Cells

“…12 Glutamate also has age-specific trophic effects in the developing cortex. 3 Although EAATs are not the only glutamate transporters expressed by CMECs, 6 the differential expression patterns of the EAATs in microvessels suggest that glutamate effects in the immature cortex are not subject to the same regulatory processes as in adulthood regarding brain-to-blood efflux. In particular, the molecular and functional specificities of mature versus immature endothelial cells with respect to EAAT expression and glutamate uptake support specific glutamate homeostasis pathways that are essential for cortical development.…”

“…1 Accumulating evidence indicates that mature microvascular endothelial cells also express EAAT1-3. 5,6 In particular, brain endothelial cells appear to control extracellular glutamate concentrations by inducing the uptake and, subsequently, the efflux of glutamate across the blood-brain barrier. 7,8 To our knowledge, EAAT1-3 expression in neonatal endothelial cells has not been studied.…”

Production of glutamic acid by Corynebacterium glutamicum using dates syrup as carbon source

“…Glutamate is mainly used as a flavor agent , recently it is known as neurotransmitter, (Hawkins, 2009). It is widely used in food, pharmaceutical, medical, biochemical and analytical industries.…”

Promising role of Carob (Ceratonia siliqua L) phytochemical components against neurotoxicity induced by monosodium glutamate

“…It is synthesized by neurons and not cross the blood-brain barrier [54]. It is responsible for maintaining developmental plasticity and memory [55]. However, intake diet containg MSG is followed by an increase in plasma glutamate level for 1 to 3 hours [56].…”