Abstract 98: Post-ischemic Intra-arterial Infusion of Liposome-encapsulated Hemoglobin Can Reduce Ischemic Reperfusion Injury

Abstract

Background: We sometimes encounter severe brain edema and hemorrhagic transformation due to ischemic reperfusion (I/R) injury after thrombolysis and/or thromboectomy. The mechanism of I/R injury is thought to depend on blood-brain barrier disruption mediated by matrix metalloproteinase-9 (MMP-9) mainly produced by circulating neutrophils. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an efficient oxygen carrier without blood cells including neutrophils, can reduce I/R injury through reducing the effect of neutrophil MMP-9 in the rat transient middle cerebral artery occlusion (MCAO) model. Methods: Male Sprague-Dawley rats were subjected to transient MCAO for 2 hours and then were divided into three groups: 1) LEH group infused with LEH (10ml/kg/h) through the recanalized internal carotid artery for 2 hours, 2) vehicle group infused with saline, and 3) control group subjected to recanalization only. After 24-hour reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, MMP-9 expression, MMP-9 activity and reactive oxygen species (ROS) production. Results: Compared with the control group, the LEH group showed significantly better neurological score (p<0.05), smaller infarct and edema size (p<0.01, p<0.05 respectively). MMP-9 expression, activity and ROS production in the LEH group were lower than those in the control group (p<0.001, p<0.01 and p<0.05, respectively). There was no significant difference between the results in the vehicle group and those in the control group. Conclusion: 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 neutrophil MMP-9. LEH may be a promising candidate to prevent I/R injury.