Therapeutic potentials of an artificial oxygen-carrier,liposome-encapsulated hemoglobin,for ischemia/reperfusion-induced cerebral dysfunction in rats

We performed this study to elucidate whether a newly developed liposome-encapsulated hemoglobin,trm-645 (trm),can prevent cerebral dysfunction resulting from acute ischemic stroke when used as an oxygen carrier. hippocampal long-term potentiation (ltp) in the perforant path-dentate gyrus synapses and anxiety-related behaviors in the elevated plus-maze test were evaluated as indices of cerebral functional outcomes in the rat with two-vessel occlusion (2vo),which was induced by 10-min clamping of bilateral common carotid arteries. saline or trm (hemoglobin concentration of 6 g/dl: 2.5 or 5 ml/kg) was administered via the tail vein immediately after ischemic insult. hippocampal ltp formation was markedly impaired and the open arm durations in the elevated plus-maze decreased significantly 4 days after 2vo,compared to those of sham-operated (control) rats,suggesting the hippocampal synaptic dysfunction and anxiogenic properties in 2vo rats. trm (5 ml/kg) restored the hippocampal ltp formation and normalized the anxiety-related behavior. trm also improved the decreased tissue oxygen partial pressure in the 2vo rat hippocampus,possibly due to oxygen delivery to ischemic regions. liposomeencapsulated hemoglobin trm might have therapeutic potentials for protecting the brain from neurological complications associated with acute ischemic stroke,as a promising blood substitute for oxygen therapy. © 2010 the japanese pharmacological society.