Abstract
We assessed the protective effects of s-nitroso (SNO)-polyethylene glycol-conjugated (PEG) hemoglobin (Hb), which was developed as an artificial oxygen carrier, after cerebral ischemia/reperfusion (I/R). Long-term potentiation (LTP) in the perforant path-dentate gyrus synapses of the rat hippocampus was evaluated as an index of functional damage after 2-vessel occlusion (2VO, 10 min). SNO-PEG-Hb, PEG-Hb, at a dose of 250 mg/kg or vehicle, was administered via tail vein. In vehicle-treated controls, 2VO produced impairment of LTP formation 4 days after ischemic insult. Marked pathological changes were not detected by light microscopy. SNO-PEG-Hb administered immediately or 24 hours after reperfusion, ameliorated the changes in LTP formation observed in vehicle-treated controls. In contrast, PEG-Hb did not exert any significant effects. Moreover, expressions of VEGF, bFGF, eNOS, iNOS and nNOS were up-regulated in the hippocampus in 2VO compared to controls. These expressions were differentially altered by SNO-Hb derivatives. Thus, it is suggested that an SNO derivative, SNO-PEG-Hb, has a beneficial effect to protect the brain from cerebral I/R damages via translocation of NO as well as NO quenching, and provides a new strategy for a pharmacological intervention against cerebral I/R. [Jpn J Physiol 54 Suppl:S42 (2004)]
