title: Augmentation of nitrite therapy in cerebral ischemia by NMDA receptor inhibition.
abstract: Our recent work suggested that early infusion of nitrite might represent a novel therapeutic approach for acute ischemic stroke. In this study, we sought to examine the therapeutic time window of nitrite in an experimental stroke model, and to develop combined strategies for augmenting its protective effects. Nitrite was infused at various times after ischemia to rats subjected to transient or permanent focal ischemia. Nitrite was infused with memantine to prevent the potential toxicity. Infarct volumes, functional outcomes, microhypoxic areas, and oxidative stress were measured. Nitrite reduced the infarction volume and enhanced functional recovery when administered within 3 and 1.5h in the transient and permanent model, respectively. Combined therapy with nitrite and memantine prolonged the time window up to 4.5h. The potential oxidative toxicities of nitrite were significantly inhibited by memantine. The combination therapy of nitrite and memantine may be a feasible therapeutic approach for acute ischemic stroke.
authors.affiliation: Department of Neurology, Stem Cell Laboratory, Clinical Research Institute, Seoul National University Hospital, 28, Yongon-dong, Chongro-gu, Seoul 110-744, South Korea.
authors.forename: Keun-Hwa
authors.initials: KH
authors.lastname: Jung
authors.forename: Kon
authors.initials: K
authors.lastname: Chu
authors.forename: Soon-Tae
authors.initials: ST
authors.lastname: Lee
authors.forename: Hee-Kwon
authors.initials: HK
authors.lastname: Park
authors.forename: Jin-Hee
authors.initials: JH
authors.lastname: Kim
authors.forename: Kyung-Muk
authors.initials: KM
authors.lastname: Kang
authors.forename: Manho
authors.initials: M
authors.lastname: Kim
authors.forename: Sang Kun
authors.initials: SK
authors.lastname: Lee
authors.forename: Jae-Kyu
authors.initials: JK
authors.lastname: Roh
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D018691:Excitatory Amino Acid Antagonists / Q000627:therapeutic use*; D008297:Male; D008559:Memantine / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D012977:Sodium Nitrite / Q000627:therapeutic use*; D020521:Stroke / Q000188:drug therapy*
chemical_list: D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D012977:Sodium Nitrite; D008559:Memantine