Post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin can reduce ischemia reperfusion injury

●The effects of post-ischemic intra-arterial infusion of LEH on I/R injury were examined.●Infusion of LEH improved neurological score and reduced infarct and edema volumes.●It also decreased MPO expression, MMP-9 expression and activity, and ROS production.●Infusion of LEH reduced the effect of MMP-9, most likely produced by neutrophils.●This therapeutic strategy may be a promising candidate for ischemic stroke.

Despite successful revascularization, reperfusion after prolonged ischemia causes ischemia reperfusion (I/R) injury. Recruitment and activation of neutrophils is thought to be a key event causing I/R injury. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier without neutrophils, could reduce I/R injury in a rat transient middle cerebral artery occlusion (MCAO) model. Male Sprague-Dawley rats were subjected to 2-h MCAO and then were divided into three groups: (1) LEH group (n=7) infused with LEH (Hb concentration of 6 g/dl, 10 ml/kg/h) through the recanalized internal carotid artery for 2 h, (2) vehicle group (n=8) infused with saline (10 ml/kg/h) in the same manner as the LEH group, and (3) control group (n=9) subjected to recanalization only. After 24-h reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, myeloperoxidase (MPO) expression, matrix metalloproteinase-9 (MMP-9) expression and activity, and reactive oxygen species (ROS) production. Compared with the control group and the vehicle group, the LEH group showed a significantly better neurological score and significantly smaller infarct and edema volumes. MPO expression, MMP-9 expression and activity, and ROS production in the LEH group were also significantly lower than those in the control and vehicle groups. The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of MMP-9, most likely produced by neutrophils. This therapeutic strategy may be a promising candidate to prevent I/R injury after thrombolysis and/or thromboectomy.