An S-Nitrosylated Hemoglobin Derivative Protects the Rat Hippocampus From Ischemia-Induced Long-Term Potentiation Impairment With a Time Window

• Main Authors: Hiroshi Otani (Author), Subrina Jesmin (Author), Hiroko Togashi (Author), Ichiro Sakuma (Author), Kunihiko Nakai (Author), Hiroshi Satoh (Author), Mitsuhiro Yoshioka (Author), Akira Kitabatake (Author)
• Format: Book
• Published: Elsevier, 2004-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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. Keywords:: S-nitrosylated hemoglobin derivative, nitric oxide, long-term potentiation, 2-vessel occlusion

Item Description

1347-8613
10.1254/jphs.fp0040385