title: Targeted delivery of extracellular matrix protected against neurologic defects after focal ischemia reperfusion in rats.
abstract: Ischemic stroke is one of the leading causes of morbidity and mortality worldwide and characterized by defective angiogenesis. The functional sequences (RGDs, GRGDSPASSPISC) derived from fibronectin have been confirmed to augment angiogenesis in vivo and in vitro. However, delivery of peptides into the brain parenchyma has been hampered by the presence of the blood-brain barrier (BBB). We fused RGDs with penetratin (Antp) derived from Drosophila antennapedia homeodomain protein to improve the penetration of peptides through BBB into ischemic hemisphere. We found Antp-RGDs successfully not only penetrate the SH-SY5Y cells but also penetrated through BBB into ischemic hemisphere by intraperitoneal injection. In addition, application of Antp-RGDs to the focal cerebral ischemic reperfusion injury in rats resulted in the reduction of cerebral ischemic volume and the improvement of neurologic score according to the 21-point score. We further demonstrated that activation of phosphorylation-extracellular-signal related kinase 1/2 (p-ERK 1/2) and upregulation of gene VEGF resulted from post-treatment with Antp-RGDs 2 hours after reperfusion onset might at least partly contribute to the benefic changes after focal cerebral ischemic reperfusion injury in rats. Our data suggested that Antp-RGDs may serve as an attractive therapeutic intervention for treating ischemic stroke.
authors.affiliation: Department of Critical-Care Medicine, Qilu Hospital of Shandong University, Shandong University, Jinan, China.
authors.forename: HongNa
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Xintai People Hospital affiliated to Taian Medical University, Xintai, China.
authors.forename: HongLing
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Thrombosis, Traffic Hospital of Shandong Province, Jinan, China.
authors.forename: YingYun
authors.initials: Y
authors.lastname: Lu
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Ma
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, China.
authors.forename: GuoYong
authors.initials: G
authors.lastname: Jia
authors.affiliation: Department of Neural Medicine, The Second Hospital of Shandong University, Shandong University, Jinan, China.
authors.forename: JianZhong
authors.initials: J
authors.lastname: Bi
authors.affiliation: Department of Neurology, Qilu Hospital of Shandong University, Shandong University, Jinan, China; Brain Science Research Institute, Shandong University, Jinan, China. Electronic address: qlyywcl@163.com.
authors.forename: CuiLan
authors.initials: C
authors.lastname: Wang
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002460:Cell Line; D016326:Extracellular Matrix Proteins / Q000008:administration & dosage / Q000627:therapeutic use*; D005353:Fibronectins / Q000627:therapeutic use; D020287:In Situ Nick-End Labeling; D002546:Ischemic Attack, Transient / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects; D008297:Male; D020768:Middle Cerebral Artery / Q000503:physiopathology; D009422:Nervous System Diseases / Q000209:etiology* / Q000517:prevention & control*; D009842:Oligopeptides / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000150:complications* / Q000188:drug therapy*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D016326:Extracellular Matrix Proteins; D005353:Fibronectins; D009842:Oligopeptides; D042461:Vascular Endothelial Growth Factor A; C047981:arginyl-glycyl-aspartic acid
keywords: Ischemia reperfusion injury; angiogenesis; fibronectin; neuroprotection; penetratin