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

Abstract

BackgroundIschemic 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 ResultsFirst, 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.ConclusionsThese 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.

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“…After observing the increased expression of paired immunoglobulin-like receptor B (PirB) in the ischemic hemisphere of mice 24 h post-MCAO, Wang et al (2018) constructed anti-PirB immunoliposome probe with a near-infrared fluorophore that was successfully applied to in vivo imaging for upregulated PirB region in a cerebral ischemic stroke model. These authors also used soluble PirB ectodomain, as a therapeutic reagent encapsulated in liposomes, showing a significant functional recovery in a model of ischemic stroke.…”