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

Journal of Pharmacological Sciences

Kunihiko Nakai¹  Hiroshi Satoh¹  Ichiro Sakuma²  Mitsuhiro Yoshioka³  Akira Kitabatake²  Hiroko Togashi³  Hiroshi Otani³  Subrina Jesmin² 

[1] Department of Environmental Health Sciences, Tohoku University Graduate School of Medicine;Department of Cardiovascular Medicine, Hokkaido University Graduate School of Medicine;Department of Neuropharmacology, Hokkaido University Graduate School of Medicine

关键词: S-nitrosylated hemoglobin derivative;    nitric oxide;    long-term potentiation;    2-vessel occlusion;   

DOI  :  10.1254/jphs.FP0040385

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(51)Cited-By(7)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.

【 授权许可】

Unknown