Liposome-encapsulated hemoglobin (LEH) has been developed as a
blood substitute. In spite of its size (1/30 - 1/40 of erythrocytes), LEH has an
oxygen-carrying capacity comparable to erythrocytes. Thus, LEH is expected to carry
oxygen into vital organs via collateral routes during
ischemia induced by vascular
embolism. In the present study, we examined the
therapeutic effects of LEH on behavioral impairments in rats after four-vessel occlusion (4VO) for 30 min. In the open-field test, locomotor activity in 4VO rats did not alter 7 days after
ischemia. However, in the contextual fear conditioning (CFC) test, the freezing rate was significantly decreased in 4VO rats, although no behavioral changes in the Y-maze test and elevated plus-maze test were observed. Phosphorylation of the
cyclic AMP response element-binding protein (CREB) in the hippocampal CA1 region after the CFC test was attenuated. These 4VO-induced impairments were significantly alleviated by the administration of LEH (5 ml/kg, i.v.) during occlusion. Moreover, LEH did not alter hippocampal blood flow and tissue
oxygen pressure during 4VO, but it did suppress
hyperoxia after
ischemia-reperfusion. These findings suggest that LEH, an artificial
oxygen carrier, could be a novel therapeutic agent for brain dysfunction after acute
cerebral ischemia.