Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex

Phillis, John W.; Smith-Barbour, M.; Perkins, L.M.; O’Regan, Michael H.

doi:10.1016/0361-9230(94)90019-1

Cited by 131 publications

(47 citation statements)

References 48 publications

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“…10 The mechanism of the initial transient phase was concluded to be reversal of the EAA transporter, and the second progressively increasing release was concluded to be a swelling-induced release. 10 In vivo, Phillis et al, 11 using a cortical superfusion system over the intact arachnoid, have shown that EAA transport or anion transport 12 blockers can partially inhibit ischemia-induced EAA release in the rat. In the present study we used microdialysis in the ischemic striatum to investigate in more detail whether both reversal of the astrocyte GLT-1 transporter and swelling-induced release contribute to ischemia-induced EAA release in vivo.…”

Section: See Editorial Comment Page 440mentioning

confidence: 99%

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

Seki

Feustel

Keller

et al. 1999

Stroke

187

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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Section: See Editorial Comment Page 440mentioning

confidence: 99%

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

Seki

Feustel

Keller

et al. 1999

Stroke

187

141

View full text Add to dashboard Cite

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“…GABA release has been attributed to exocytosis dependent on extracellular Ca 2ϩ (Djali and Dawson, 2001), to leak through ruptured cell membranes (Phillis et al, 1994), or to reversal of Na ϩ -dependent GABA transporters (Zeevalk and Nicklas, 1996;Saransaari and Oja, 1997). We have, therefore, reinvestigated the mode of release of GABA and its effects when the hippocampus is exposed to simulated ischemia.…”

Section: Introductionmentioning

confidence: 99%

Sequential Release of GABA by Exocytosis and Reversed Uptake Leads to Neuronal Swelling in Simulated Ischemia of Hippocampal Slices

Allen¹,

Rossi²,

Attwell³

2004

J. Neurosci.

106

115

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GABA release during cerebral energy deprivation (produced by anoxia or ischemia) has been suggested either to be neuroprotective, because GABA will hyperpolarize neurons and reduce release of excitotoxic glutamate, or to be neurotoxic, because activation of GABA A receptors facilitates Cl Ϫ entry into neurons and consequent cell swelling. We have used the GABA A receptors of hippocampal area CA1 pyramidal cells to sense the rise of [GABA] o occurring in simulated ischemia. Ischemia evoked, after several minutes, a large depolarization to ϳϪ20 mV. Before this "anoxic depolarization," there was an increase in GABA release by exocytosis (spontaneous IPSCs). After the anoxic depolarization, there was a much larger, sustained release of GABA that was not affected by blocking action potentials, vesicular release, or the glial GABA transporter GAT-3 but was inhibited by blocking the neuronal GABA transporter GAT-1. Blocking GABA A receptors resulted in a more positive anoxic depolarization but decreased cell swelling at the time of the anoxic depolarization. The influence of GABA A receptors diminished in prolonged ischemia because glutamate release evoked by the anoxic depolarization inhibited GABA A receptor function by causing calcium entry through NMDA receptors. These data show that ischemia releases GABA initially by exocytosis and then by reversal of GAT-1 transporters and that the resulting Cl Ϫ influx through GABA A receptor channels causes potentially neurotoxic cell swelling.

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“…The uptake of glutamate by sodium-dependent glutamate transporters such as astrocytic GLT-1 is driven by the co-transport of three sodium ions and one proton with each glutamate ion into the cell, while one potassium ion is transported out of the cell (5)(6)(7). During ischemia, the activity of Na + ,K + -ATPase is markedly suppressed, resulting in the accumulation of intracellular sodium ions (8).…”

Section: Introductionmentioning

confidence: 99%

“…It has been postulated that the excessive influx of Na + into astroglial cells causes significant astroglial cell death (10) due to Ca 2+ overload probably via a reversed Na + /Ca 2+ exchanger. Therefore, there is a possibility that the 5 ischemia-induced reverse mode operation of GLT-1 contributes to the survival of astrocytes themselves by reducing Na + overload, although the reversal causes massive neuronal death.…”

Section: Introductionmentioning

confidence: 99%

Reversed Actrocytic GLT-1 during Ischemia is Crucial to Excitotoxic Death of Neurons, but Contributes to the Survival of Astrocytes themselves

Kosugi

Kikuchi

2006

Neurochem Res

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During ischemia, the operation of astrocytic/neuronal glutamate transporters is reversed and glutamate and Na + are co-transported to the extracellular space. This study aims to investigate whether this reversed operation of glutamate transporters has any functional meanings for astrocytes themselves. Oxygen/glucose deprivation (OGD) of neuron/astrocyte co-cultures resulted in the massive death of neurons, and the cell death was significantly reduced by treatment with either AP5 or DHK. In cultured astrocytes with little GLT-1 expression, OGD produced Na + overload, resulting in the reversal of astrocytic Na + /Ca 2+ -exchanger (NCX). The reversed NCX then caused Ca 2+ overload leading to the damage of astrocytes. In contrast, the OGD-induced Na + overload and astrocytic damage were significantly attenuated in PACAP-treated astrocytes with increased GLT-1 expression, and the attenuation was antagonized by treatment with DHK. These results suggested that the OGD-induced reversal of GLT-1 contributed to the survival of astrocytes themselves by releasing Na + with glutamate via reversed GLT-1.

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Characterization of glutamate, aspartate, and GABA release from ischemic rat cerebral cortex

Cited by 131 publications

References 48 publications

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

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

Sequential Release of GABA by Exocytosis and Reversed Uptake Leads to Neuronal Swelling in Simulated Ischemia of Hippocampal Slices

Reversed Actrocytic GLT-1 during Ischemia is Crucial to Excitotoxic Death of Neurons, but Contributes to the Survival of Astrocytes themselves

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