Abstract
Heme-degradation after erythrocyte lysis plays an important role in the pathophysiology of intracerebral hemorrhage. Low-density lipoprotein receptor-related protein-1 is a receptor expressed predominately at the neurovascular interface, which facilitates the clearance of the hemopexin and heme complex. In the present study, we investigated the role of low-density lipoprotein receptor-related protein-1 in heme removal and neuroprotection in a mouse model of intracerebral hemorrhage. Endogenous low-density lipoprotein receptor-related protein-1 and hemopexin were increased in ipsilateral brain after intracerebral hemorrhage, accompanied by increased hemoglobin levels, brain water content, blood-brain barrier permeability and neurological deficits. Exogenous human recombinant low-density lipoprotein receptor-related protein-1 protein reduced hematoma volume, brain water content surrounding hematoma, blood-brain barrier permeability and improved neurological function three days after intracerebral hemorrhage. The expression of malondialdehyde, fluoro-Jade C positive cells and cleaved caspase 3 was increased three days after intracerebral hemorrhage in the ipsilateral brain tissues and decreased with recombinant low-density lipoprotein receptor-related protein-1. Intracerebral hemorrhage decreased and recombinant low-density lipoprotein receptor-related protein-1 increased the levels of superoxide dismutase 1. Low-density lipoprotein receptor-related protein-1 siRNA reduced the effect of human recombinant low-density lipoprotein receptor-related protein-1 on all outcomes measured. Collectively, our findings suggest that low-density lipoprotein receptor-related protein-1 contributed to heme clearance and blood-brain barrier protection after intracerebral hemorrhage. The use of low-density lipoprotein receptor-related protein-1 as supplement provides a novel approach to ameliorating intracerebral hemorrhage brain injury via its pleiotropic neuroprotective effects.
Original language | English |
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Pages (from-to) | 1299-1310 |
Number of pages | 12 |
Journal | Journal of Cerebral Blood Flow and Metabolism |
Volume | 37 |
Issue number | 4 |
DOIs | |
State | Published - Apr 2017 |
ASJC Scopus Subject Areas
- Neurology
- Clinical Neurology
- Cardiology and Cardiovascular Medicine
Keywords
- Blood-brain barrier permeability
- Brain edema
- Heme scavenging
- Intracerebral hemorrhage
- Low-density lipoprotein receptor-related protein-1
- Neuroprotective Agents/administration & dosage
- Heme/metabolism
- Male
- Recombinant Proteins
- Capillary Permeability/drug effects
- Mice, Inbred Strains
- Animals
- Hemopexin/metabolism
- Receptors, LDL/administration & dosage
- Behavior, Animal/drug effects
- Blood-Brain Barrier/drug effects
- Cerebral Hemorrhage/drug therapy
- Low Density Lipoprotein Receptor-Related Protein-1
- Tumor Suppressor Proteins/administration & dosage