title: Glutamate transporters in brain ischemia: to modulate or not?
abstract: In this review, we briefly describe glutamate (Glu) metabolism and its specific transports and receptors in the central nervous system (CNS). Thereafter, we focus on excitatory amino acid transporters, cystine/glutamate antiporters (system xc-) and vesicular glutamate transporters, specifically addressing their location and roles in CNS and the molecular mechanisms underlying the regulation of Glu transporters. We provide evidence from in vitro or in vivo studies concerning alterations in Glu transporter expression in response to hypoxia or ischemia, including limited human data that supports the role of Glu transporters in stroke patients. Moreover, the potential to induce brain tolerance to ischemia through modulation of the expression and/or activities of Glu transporters is also discussed. Finally we present strategies involving the application of ischemic preconditioning and pharmacological agents, eg β-lactam antibiotics, amitriptyline, riluzole and N-acetylcysteine, which result in the significant protection of nervous tissues against ischemia.
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Weronika
authors.initials: W
authors.lastname: Krzyżanowska
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Pomierny
authors.affiliation: Department of Toxicology, Faculty of Pharmacy, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Magłorzata
authors.initials: M
authors.lastname: Filip
authors.affiliation: Department of Neurology, Jagiellonian University, Medical College, Krakow, Poland.
authors.forename: Joanna
authors.initials: J
authors.lastname: Pera
mesh_terms: D026922:Amino Acid Transport Systems, Acidic / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D050491:Glutamate Plasma Membrane Transport Proteins / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D006801:Humans; D019194:Ischemic Preconditioning; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D009435:Synaptic Transmission / Q000187:drug effects; D016896:Treatment Outcome; D050496:Vesicular Glutamate Transport Proteins / Q000187:drug effects* / Q000378:metabolism
chemical_list: D026922:Amino Acid Transport Systems, Acidic; D050491:Glutamate Plasma Membrane Transport Proteins; D018696:Neuroprotective Agents; D050496:Vesicular Glutamate Transport Proteins; D018698:Glutamic Acid