title: Attenuated effects of Neu2000 on hypoxia-induced synaptic activities in a rat hippocampus.
abstract: Neu2000 (NEU; 2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)-benzoic acid), a recently developed derivative of acetylsalicylic acid and sulfasalazine, potently protects against neuronal cell death following ischemic brain injury by antagonizing NMDA receptor-mediated neuronal toxicity and oxidative stress. However, it has yet to be determined whether NEU can attenuate hypoxia-induced impairment of neuronal electrical activity. In this study, we carried out extracellular recordings of hippocampal slices in order to investigate the effects of NEU on the electrical activity of neurons exposed to a hypoxic insult (oxygen and glucose deprivation). NEU prominently suppressed hypoxia-induced impairment of neuronal activity in a concentration-dependent manner. NEU, at a low dose (1 μM), competently depressed the hypoxia-induced convulsive activity in a manner similar to trolox. Furthermore, high concentrations of NEU (50 μM) markedly abolished all hypoxia-mediated impairment of neuronal activity and accelerated the slow recovery of neuronal activity more efficiently than ifenprodil and APV. These results suggest that NEU attenuates hypoxia-induced impairment of neuronal activity more potently than the antioxidant, trolox, and the NMDA receptor antagonists, ifenprodil and APV. We propose that NEU is a striking pharmacological candidate for neuroprotection against hypoxia because of its defensive action on hypoxia-mediated impairment of electrical neurotransmission as well as its neuroprotective action against neuronal cell death induced by exposure to pathological hypoxic conditions.
authors.affiliation: Department of Brain and Cognitive Sciences, Ewha Womans University, Daehyun-dong, Seodaemun-Gu, Seoul, 120-750, South Korea.
authors.forename: Jihyun
authors.initials: J
authors.lastname: Noh
authors.forename: Young-Hyun
authors.initials: YH
authors.lastname: Koh
authors.forename: Jun-Mo
authors.initials: JM
authors.lastname: Chung
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D056654:CA3 Region, Hippocampal / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D005464:Fluorobenzenes / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D008839:Microelectrodes; D009474:Neurons / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012459:Salicylates / Q000494:pharmacology*; D009435:Synaptic Transmission / Q000187:drug effects*; D062368:meta-Aminobenzoates / Q000494:pharmacology*
chemical_list: C519903:2-hydroxy-5-(2,3,5,6-tetrafluoro-4-trifluoromethyl-benzylamino)benzoic acid; D000975:Antioxidants; D005464:Fluorobenzenes; D018696:Neuroprotective Agents; D012459:Salicylates; D062368:meta-Aminobenzoates; D005947:Glucose; D010100:Oxygen