Neuronal PirB Upregulated in Cerebral Ischemia Acts as an Attractive Theranostic Target for Ischemic Stroke.

Abstract

BACKGROUND:

Ischemic stroke is a complex disease with multiple etiologies and clinical manifestations. Paired immunoglobulin-like receptor B (PirB), which is originally thought to function exclusively in the immune system, is now also known to be expressed by neurons. A growing number of studies indicate that PirB can inhibit neurite outgrowth and restrict neuronal plasticity. The aim of the study is to investigate whether PirB can be an attractive theranostic target for ischemic stroke.

METHODS AND RESULTS:

First, we investigated the spatial-temporal expression of PirB in multiple ischemic stroke models, including transient middle cerebral artery occlusion, photothrombotic cerebral cortex ischemia, and the neuronal oxygen glucose deprivation model. Then, anti-PirB immunoliposome nanoprobe was developed by thin-film hydration method and investigated its specific targeting in vitro and in vivo. Finally, soluble PirB ectodomain (sPirB) protein delivered by polyethylene glycol-modified nanoliposome was used as a therapeutic reagent for ischemic stroke by blocking PirB binding to its endogenous ligands. These results showed that PirB was significantly upregulated after cerebral ischemic injury in ischemic stroke models. Anti-PirB immunoliposome nanoprobe was successfully developed and specifically bound to PirB in vitro. There was accumulation of anti-PirB immunoliposome nanoprobe in the ischemic hemisphere in vivo. Soluble PirB ectodomains remarkably improved ischemic stroke model recovery by liposomal delivery system.

CONCLUSIONS:

These data indicated that PirB was a significant element in the pathological process of cerebral ischemia. Therefore, PirB may act as a novel theranostic target for ischemic stroke.

• Authors: Jie Wang, Ying Zhang, Jing Xia, Tingting Cai, Jiawei Du, Jinpeng Chen, Ping Li, Yuqing Shen, Aifeng Zhang, Bo Fu, Xueren Gao, Fenqin Miao, Jianqiong Zhang, Gaojun Teng
• Journal: Journal of the American Heart Association (J Am Heart Assoc) Vol. 7 Issue 3 (01 29 2018) ISSN: 2047-9980 [Electronic] England
• PMID: 29378731 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

Chemical References

• Biomarkers
• Ligands
• Liposomes
• Peptide Fragments
• Pirb protein, mouse
• Receptors, Immunologic

Topics

• Animals
• Apoptosis
• Biomarkers (metabolism)
• Brain (diagnostic imaging, metabolism, pathology, physiopathology)
• Cells, Cultured
• Infarction, Middle Cerebral Artery (diagnostic imaging, metabolism, pathology, therapy)
• Ligands
• Liposomes
• Magnetic Resonance Imaging
• Male
• Mice, Inbred C57BL
• Molecular Imaging (methods)
• Nanoparticles
• Neurons (metabolism, pathology)
• Peptide Fragments (administration & dosage, metabolism)
• Protein Binding
• Protein Interaction Domains and Motifs
• Receptors, Immunologic (administration & dosage, genetics, metabolism)
• Recovery of Function
• Spectroscopy, Near-Infrared
• Theranostic Nanomedicine (methods)
• Time Factors
• Up-Regulation