Abstract 19922: Phosphatidylserine Receptor Upregulation in Stroke for Targeted Carrier Delivery
Introduction: The phosphatidylserine receptor (PSR) plays an important role in apoptosis and inflammation. Whether this receptor is expressed in damaged brain cells in the early stages of stroke is unknown.
Hypothesis: The purpose of this study was to determine if this receptor is expressed on ischemic neurovascular endothelial cells and if so, can it bind with PS-containing liposomes (PS-liposomes). The latter would allow for a neurovascular targeting strategy for therapeutic delivery to ischemic brain cells.
Methods: Sprague Dawley rats (n=22) were randomly divided into sham, cerebral ischemia, and subarachnoid hemorrhage (SAH) injury groups. Cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 hours using an intraluminal suture method. SAH was induced by an endovascular perforation method. Brain tissue was harvested for immunofluorescence staining at day 2 after surgery. Cultured human umbilical vein endothelial cells (HUVEC) were pre-treated with tumor necrosis factor alpha (TNFα) to stimulated PSR. Fluorescence labeled PS-containing liposomes (FITC-PS-Liposomes) were used. The PSR expression and the adhesion of liposomes were observed using fluorescence microscopy.
Results: Normal brain tissue did not demonstrate PSR expression (Fig.1A). After brain injury, PSR expression was observed in the injured area and colocalized with the endothelium both in the MCAO (Fig.1B) and SAH animals (Fig.1C). Normal HUVEC did not demonstrate fluorescence (Fig.1D). Weak fluorescence was observed in normal cells that incorporated the PS-liposomes (Fig.1E). Strong fluorescence was observed in the TNFα-activated HUVEC that incorporated the FITC-PS-Liposomes (Fig.1F).
Conclusions: This is first report that PSR expression occurs in cerebral microvascular endothelial cells in the early stages of stroke and can be recognized by PS-liposomes. This may allow development of a targeted liposomal carrier for novel targeted stroke treatment.
Author Disclosures: T. Peng: None. D.D. McPherson: None. S. Huang: None.
- © 2015 by American Heart Association, Inc.