Hemopexin reduces blood–brain barrier injury and protects synaptic plasticity in cerebral ischemic rats by promoting EPCs through the HO-1 pathway

Abstract

Ischemic stroke causes endothelial dysfunction and blood–brain barrier dysfunction, thus damages synaptic plasticity such as learning and memory. In this study we aim to investigate the effect of hemopexin (HPX) in protecting synaptic plasticity and blood brain barrier integrity from toxic heme, and determine whether this effect is via the activation of endothelial progenitor cells (EPCs) through the heme oxygenase-1 (HO-1) pathway. Our data indicates HPX showed a significant effect in inducing the expression of HO-1, promoting the migration and differentiation of EPCs, facilitating new blood vessel formation thus protecting blood–brain barrier integrity. Also the magnitude of synaptic plasticity of rats recovered with HPX treatment. And in the presence of HO-1 blocker Zinc protoporphyrin-9 (ZnppIX), HPX lost its protective effect. This suggests that HPX protects endothelial and blood brain barrier integrity from toxic heme, thus protects neurologic function in cerebral ischemic rats in HO-1 pathway.