Inhibition of Blood-Brain Barrier Disruption by an Apolipoprotein E-Mimetic Peptide Ameliorates Early Brain Injury in Experimental Subarachnoid Hemorrhage

• Published in: Translational stroke research Vol. 8; no. 3; pp. 257 - 272
• Main Authors: Pang, Jinwei, Chen, Yitian, Kuai, Li, Yang, Ping, Peng, Jianhua, Wu, Yue, Chen, Yue, Vitek, Michael P., Chen, Ligang, Sun, Xiaochuan, Jiang, Yong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2017; Springer Nature B.V
• Subjects: Animals; Apolipoproteins; Apolipoproteins E - metabolism; Apolipoproteins E - therapeutic use; Apoptosis; Apoptosis - drug effects; Biomedical and Life Sciences; Biomedicine; Blood-brain barrier; Blood-Brain Barrier - drug effects; Blood-Brain Barrier - metabolism; Brain Edema - drug therapy; Brain Edema - metabolism; Brain Injuries - drug therapy; Cardiology; Disease Models, Animal; Edema; Glucose; Hemorrhage; Labeling; Laboratory animals; Lectins; Male; Mice, Inbred C57BL; Monoclonal antibodies; Neurology; Neuroprotective Agents - therapeutic use; Neurosciences; Neurosurgery; NF-kappa B - metabolism; Original Article; Peptides; Polyclonal antibodies; Positron Emission Tomography Computed Tomography - methods; Proteins; Subarachnoid Hemorrhage - drug therapy; Transmission electron microscopy; Traumatic brain injury; Variance analysis; Vascular Surgery; United Kingdom > UK; United States > US; China; Early brain injury; Blood-brain barrier; Subarachnoid hemorrhage; ApoE-mimetic peptide; Apoptosis
• ISSN: 1868-4483; 1868-601X
• DOI: 10.1007/s12975-016-0507-1

Apolipoprotein E (ApoE)-mimetic peptides have been demonstrated to be beneficial in secondary brain injury following experimental subarachnoid hemorrhage (SAH). However, the molecular mechanisms underlying these benefits in SAH models have not been clearly identified. This study investigated whether an ApoE-mimetic peptide affords neuroprotection in early brain injury (EBI) following SAH by attenuating BBB disruption. SAH was induced by an endovascular perforation in young, healthy, male wild-type (WT) C57BL/6J mice. Multiple techniques, including MRI with T2-weighted imaging, 18 FDG PET-CT scanning and histological studies, were used to examine BBB integrity and neurological dysfunction in EBI following SAH. We found that SAH induced a significant increase of BBB permeability and neuron apoptosis, whereas ApoE-mimetic peptide treatment significantly reduced the degradation of tight junction proteins and endothelial cell apoptosis. These effects reduced brain edema and neuron apoptosis, increased cerebral glucose uptake, and improved neurological functions. Further investigation revealed that the ApoE-mimetic peptide inhibited the proinflammatory activators of MMP-9, including CypA, NF-κB, IL-6, TNF-α, and IL-1β, thereby ameliorating BBB disruption at the acute stage of SAH. Together, these data indicate that ApoE-mimetic peptide may be a novel and promising therapeutic strategy for EBI amelioration after SAH that are worthy of further study.