An S-nitrosylated hemoglobin derivative protects the rat hippocampus from ischemia-induced long-term potentiation impairment with a time window

Hiroshi Otani, Subrina Jesmin, Hiroko Togashi, Ichiro Sakuma, Kunihiko Nakai, Hiroshi Satoh, Mitsuhiro Yoshioka, Akira Kitabatake

Research output: Contribution to journalArticlepeer-review

9 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)188-198
Number of pages11
JournalJournal of Pharmacological Sciences
Volume96
Issue number2
DOIs
Publication statusPublished - 2004 Oct

Keywords

  • 2-vessel occlusion
  • Long-term potentiation
  • Nitric oxide
  • S-nitrosylated hemoglobin derivative

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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