S-Nitrosylated Pegylated Hemoglobin Reduces the Size of Cerebral Infarction in Rats
Tokai University School of Medicine, Isehara, Kanagawa, Japan.Artificial Organs (Impact Factor: 2.05). 03/2009; 33(2):183-8. DOI: 10.1111/j.1525-1594.2008.00705.x
Cell-free hemoglobin-based oxygen carriers have well-documented safety and efficacy problems such as nitric oxide (NO) scavenging and extravasation that preclude clinical use. To counteract these effects, we developed S-nitrosylated pegylated hemoglobin (SNO-PEG-Hb, P(50) = 12 mm Hg) and tested it in a brain ischemia and reperfusion model. Neurological function and extent of cerebral infarction was determined 24 h after photochemically induced thrombosis of the middle cerebral artery in the rat. Infarction extent was determined from the integrated area in the cortex and basal ganglia detected by triphenyltetrazolium chloride staining in rats receiving various doses of SNO-PEG-Hb (2, 0.4, and 0.08 mL/kg) and compared with rats receiving pegylated hemoglobin without S-nitrosylation (PEG-Hb) or saline of the same dosage. Results indicated that successive dilution revealed SNO-PEG-Hb but not PEG-Hb to be effective in reducing the size of cortical infarction but not neurological function at a dose of 0.4 mL/kg. In conclusion, SNO-PEG-Hb in a dose of 0.4 mL/kg (Hb 24 mg/kg) showed to be most effective in reducing the size of cortical infarction, however, without functional improvement.
- Artificial Organs 03/2009; 33(2):97-9. DOI:10.1111/j.1525-1594.2008.00692.x · 2.05 Impact Factor
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ABSTRACT: Polyethylene glycol-conjugated hemoglobin (PEG-Hb) has been proposed as a blood substitute for transfusion due to their plasma expansion and oxygen transport capabilities. The protective effect of PEG-Hb on cerebral hypoxic-ischemic injury was investigated in neonatal hypoxia model and adult rat focal cerebral ischemia model. As intravenously administered 30 min before the onset of hypoxia, PEG-Hb markedly protected cerebral hypoxic injury in a neonatal rat hypoxia model. A similar treatment of PEG-Hb largely reduced the ischemic injury ensuing after 2-h middle cerebral artery occlusion followed by 22-h reperfusion. Consistently, neurological disorder was significantly improved by PEG-Hb. The results indicate that the pharmacological blockade of cerebral ischemic injury by using PEG-Hb may provide a useful strategy for the treatment of cerebral stroke.Biomolecules and Therapeutics 07/2009; 17(3):270-275. DOI:10.4062/biomolther.2009.17.3.270 · 1.73 Impact Factor
- Artificial Organs 03/2010; 34(3):242-66. DOI:10.1111/j.1525-1594.2010.01014.x · 2.05 Impact Factor
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