Inability of volatile anesthetics to inhibit oxygen-glucose deprivation-induced glutamate release via glutamate transporters and anion channels in rat corticostriatal slices.
Ischemia-induced extracellular glutamate accumulation and the subsequent excitotoxicity contribute significantly to ischemic brain injury. Volatile anesthetics have been shown to reduce ischemic brain injury. Here, we showed that oxygen-glucose deprivation (OGD, to simulate ischemia in vitro) increased extracellular glutamate accumulation in the corticostriatal slices of adult rats. This increased accumulation was reduced by dihydrokinate, a glutamate transporter type 2 inhibitor, and 4,4'-dinitrostilbene-2,2'-disulfonic acid, a blocker for volume-activated anion channels. The volatile anesthetics isoflurane, sevoflurane and desflurane at clinically relevant concentrations did not affect the OGD-induced extracellular glutamate accumulation from brain slices of adult rats. Isoflurane also did not change the OGD-induced extracellular glutamate accumulation from brain slices of newborn/young rats. These results suggest that the OGD-induced glutamate accumulation involves reversed transport of glutamate via glutamate transporters and volume-activated anion channels. Volatile anesthetics may not inhibit this extracellular glutamate accumulation.
Jung
Hae-Hyuk
HH
Department of Anesthesiology, University of Virginia Health System, 1 Hospital Drive, PO Box 800710, Charlottesville, Virginia 22908-0710, USA.
Lee
Jeong Jin
JJ
Washington
Jacqueline M
JM
Zuo
Zhiyi
Z
D027322:Amino Acid Transport System X-AG / Q000037:antagonists & inhibitors / Q000502:physiology*; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000838:Anions / Q000378:metabolism; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D015687:Cell Hypoxia; D002851:Chromatography, High Pressure Liquid; D000077335:Desflurane; D004791:Enzyme Inhibitors / Q000494:pharmacology; D027342:Excitatory Amino Acid Transporter 2 / Q000037:antagonists & inhibitors / Q000502:physiology; D045604:Extracellular Fluid / Q000187:drug effects / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D018698:Glutamic Acid / Q000378:metabolism*; D066298:In Vitro Techniques; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D007530:Isoflurane / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D010100:Oxygen / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D000077149:Sevoflurane; D013267:Stilbenes / Q000494:pharmacology
D027322:Amino Acid Transport System X-AG; D018685:Anesthetics, Inhalation; D000838:Anions; D004791:Enzyme Inhibitors; D027342:Excitatory Amino Acid Transporter 2; D007473:Ion Channels; D008738:Methyl Ethers; D013267:Stilbenes; D000077149:Sevoflurane; D018698:Glutamic Acid; C022306:4,4'-dinitro-2,2'-stilbenedisulfonic acid; D000077335:Desflurane; D007530:Isoflurane; D005947:Glucose; D010100:Oxygen