Ischemic disruption of glutamate homeostasis in brain: quantitative immunocytochemical analyses

Ottersen, Ole Petter; Laake, Jon Henrik; Reichelt, Winfried; Haug, Finn‐Mogens Šmejda; Torp, Reidun

doi:10.1016/s0891-0618(96)00178-0

Cited by 60 publications

(42 citation statements)

References 71 publications

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“…Either through the Ca 2+ -dependant and vesicular mode or through the reversed operation of glutamate transporters, NMDA receptors or G-protein pathway (Jabaudon et al, 2000;Rossi et al, 2000). The reversed uptake mechanism and the neuronal glutamate-pool is believed to dominate during ischemia (Ottersen et al, 1996;Danbolt, 2001). There is an increased xanthine oxidase (XO) activity after traumatic brain injury.…”

Section: Discussionmentioning

confidence: 99%

Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats

Chandrashekhar

Ranpariya

Ganapaty

et al. 2010

Journal of Ethnopharmacology

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Section: Discussionmentioning

confidence: 99%

Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats

Chandrashekhar

Ranpariya

Ganapaty

et al. 2010

Journal of Ethnopharmacology

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“…30 Continued uptake by astrocytes during ischemia was suggested to explain this observation. 30 Since there cannot be both increased net uptake and release by the same transporter, one would need to postulate additional net intracellular generation of glutamate in astrocytes in ischemia either from glutamine or through a transamination reaction. 31 …”

Section: Seki Et Al February 1999 437mentioning

confidence: 96%

Inhibition of Ischemia-Induced Glutamate Release in Rat Striatum by Dihydrokinate and an Anion Channel Blocker

Seki

Feustel

Keller

et al. 1999

Stroke

186

141

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Background and Purpose-Increased activation of excitatory amino acid (EAA) receptors is considered a major cause of neuronal damage. Possible sources and mechanisms of ischemia-induced EAA release were investigated pharmacologically with microdialysis probes placed bilaterally in rat striatum. Methods-Forebrain ischemia was induced by bilateral carotid artery occlusion and controlled hypotension in halothaneanesthetized rats. During 30 minutes of ischemia, microdialysate concentrations of glutamate and aspartate were measured in the presence of a nontransportable blocker of the astrocytic glutamate transporter GLT-1, dihydrokinate (DHK), or an anion channel blocker, 4,4Ј-dinitrostilben-2,2Ј-disulfonic acid (DNDS), administered separately or together through the dialysis probe. Results-In control striata during ischemia, glutamate and aspartate concentrations increased 44Ϯ13 (meanϮSEM) times and 19Ϯ5 times baseline, respectively, and returned to baseline values on reperfusion. DHK (1 mmol/L in perfusate; nϭ8) significantly attenuated EAA increases compared with control (glutamate peak, 9.6Ϯ1.7 versus control, 15.4Ϯ2.6 pmol/L). EAA levels were similarly decreased by 10 mmol/L DHK. DNDS (1 mmol/L; nϭ5) also suppressed EAA peak increases (glutamate peak, 5.8Ϯ1.1 versus control, 10.1Ϯ0.7 pmol/L). At a higher concentration, DNDS (10 mmol/L; nϭ7) further reduced glutamate and aspartate release and also inhibited ischemia-induced taurine release.

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“…Although terminals are generally believed to have much higher glutamate levels than astrocytes, there is, as far as we are aware of, no comprehensive overview of the glutamate concentrations in the various cellular compartments in different brain regions of wildtype animals. It is, however, possible to do some very rough estimates by combining histology data from normal rats (Nafstad and Blackstad, 1966;Lehre and Danbolt, 1998) with available information on glutamate distribution (Ottersen, 1989;Storm-Mathisen and Ottersen, 1990;Torp et al, 1991;Storm-Mathisen et al, 1992;Ottersen et al, 1992;Ottersen et al, 1996). Based on this studies is seems reasonable to conclude that around 10 % of tissue glutamate is in astroglia, 70 % in glutamatergic nerve terminals and the remainder in other parts of the neurons.…”

Section: Heteroexchange Is Not Substantially Faster Than Net Uptakementioning

confidence: 98%

Neuronal vs glial glutamate uptake: Resolving the conundrum

Danbolt

Furness

Zhou

2016

Neurochemistry International

172

152

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Neither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that both astrocytes and neurons express glutamate transporters. However, the relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) a hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox. ABBREVIATIONSCre, Cyclization recombinase (Le and Sauer, 2000); EAAC1, glutamate transporter (EAAT3; slc1a1; Kanai and Hediger, 1992; Bjørås et al., 1996); EAAT, excitatory amino acid transporter (synonym to glutamate transporter); GABA, γ-aminobutyric acid; GLAST, rat glutamate transporter (EAAT1; slc1a3; Storck et al., 1992;Tanaka, 1993a); GLT-1, rat glutamate transporter (EAAT2; slc1a2; Pines et al., 1992); GLUL, glutamine synthetase; TBOA, DL-threo-β-benzyloxyaspartate AbstractNeither normal brain function nor the pathological processes involved in neurological diseases can be adequately understood without knowledge of the release, uptake and metabolism of glutamate. The reason for this is that glutamate (a) is the most abundant amino acid in the brain, (b) is at the cross-roads between several metabolic pathways, and (c) serves as the major excitatory neurotransmitter. In fact most brain cells express glutamate receptors and are thereby influenced by extracellular glutamate. In agreement, brain cells have powerful uptake systems that constantly remove glutamate from the extracellular fluid and thereby limit receptor activation. It has been clear since the 1970s that astrocytes and neurons express glutamate transporters. The relative contribution of neuronal and glial transporters to the total glutamate uptake activity, however, as well as their functional importance, has been hotly debated ever since. The present short review provides (a) an overview of what we know about neuronal glutamate uptake as well as an historical description of how we got there, and (b) an hypothesis reconciling apparently contradicting observations thereby possibly resolving the paradox.

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Ischemic disruption of glutamate homeostasis in brain: quantitative immunocytochemical analyses

Cited by 60 publications

References 71 publications

Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats

Neuroprotective activity of Matricaria recutita Linn against global model of ischemia in rats

Inhibition of Ischemia-Induced Glutamate Release in Rat Striatum by Dihydrokinate and an Anion Channel Blocker

Neuronal vs glial glutamate uptake: Resolving the conundrum

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