title: An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window.
abstract: Evidence suggests that S-nitrosylation is a biological process involved in cerebral ischemia. The aim of the present study was to elucidate the effects of S-nitrosylated (SNO) polyethylene glycol-conjugated (PEG) hemoglobin (Hb) developed as an artificial oxygen carrier, which can absorb free NO and translocate NO to a sulfhydryl (SH) moiety, on ischemic cerebral dysfunction. Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as functional outcome 4 days after transient incomplete cerebral ischemia (2-vessel occlusion: 2VO, 10 min). SNO-PEG-Hb (250 mg/kg, i.v.) administered on Day 0, 1, 2, or 4 (immediately, 24 h, 48 h, or 96 h after reperfusion, respectively) alleviated 2VO-induced LTP impairment with a therapeutic time window. The effect was significant when SNO-PEG-Hb was administered on Day 1 or 2. SNO-PEG-Hb altered NOS features observed in the vehicle-treated 2VO rat, upregulation of eNOS, nNOS, and iNOS expressions at mRNA and protein levels; SNO-PEG-Hb further upregulated eNOS and nNOS and downregulated iNOS expressions. These findings suggest that SNO-PEG-Hb might have protective effects on the rat hippocampus from ischemia/reperfusion-induced functional damages, thereby increasing the therapeutic potential as an artificial oxygen carrier for use in the area of oxygen therapy.
authors.affiliation: Department of Neuropharmacology, Hokkaido University Graduate School of Medicine, Sapporo 060-8638, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Otani
authors.forename: Subrina
authors.initials: S
authors.lastname: Jesmin
authors.forename: Hiroko
authors.initials: H
authors.lastname: Togashi
authors.forename: Ichiro
authors.initials: I
authors.lastname: Sakuma
authors.forename: Kunihiko
authors.initials: K
authors.lastname: Nakai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Satoh
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Yoshioka
authors.forename: Akira
authors.initials: A
authors.lastname: Kitabatake
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000378:metabolism; D006454:Hemoglobins / Q000494:pharmacology / Q000627:therapeutic use*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D017774:Long-Term Potentiation / Q000187:drug effects* / Q000502:physiology; D008297:Male; D019001:Nitric Oxide Synthase / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
chemical_list: D006454:Hemoglobins; C103574:S-nitrosohemoglobin; D019001:Nitric Oxide Synthase