title: Blockade of microglial glutamate release protects against ischemic brain injury.
abstract: Glutamate released by activated microglia induces excito-neurotoxicity and may contribute to neurodegeneration in numerous neurological diseases including ischemia, inflammation, epilepsy, and neurodegenerative diseases. We observed that the gap junction blocker carbenoxolone (CBX) or the glutaminase inhibitor 6-diazo-5-oxo-L-norleucine (DON) decreased glutamate release from activated microglia and rescued neuronal death in a dose-dependent manner in vitro. In gerbils, treatment with CBX or DON also prevented the delayed death of hippocampal neurons following transient global ischemia. Thus, blockade of microglial glutamate release may be an effective therapeutic strategy against neurodegeneration after ischemic injury.
authors.affiliation: Department of Neuroimmunology, Research Institute of Environmental Medicine, Nagoya University, Nagoya, Japan. htake@riem.nagoya-u.ac.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Takeuchi
authors.forename: Shijie
authors.initials: S
authors.lastname: Jin
authors.forename: Hiromi
authors.initials: H
authors.lastname: Suzuki
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Doi
authors.forename: Jianfeng
authors.initials: J
authors.lastname: Liang
authors.forename: Jun
authors.initials: J
authors.lastname: Kawanokuchi
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Mizuno
authors.forename: Makoto
authors.initials: M
authors.lastname: Sawada
authors.forename: Akio
authors.initials: A
authors.lastname: Suzumura
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D002229:Carbenoxolone / Q000494:pharmacology; D003980:Diazooxonorleucine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017629:Gap Junctions / Q000187:drug effects; D005849:Gerbillinae; D018698:Glutamic Acid / Q000378:metabolism*; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000378:metabolism*; D009410:Nerve Degeneration / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology
chemical_list: D003980:Diazooxonorleucine; D018698:Glutamic Acid; D002229:Carbenoxolone