title: Receptor-associated protein promotes t-PA expression, reduces PAI-1 expression and improves neurorecovery after acute ischemic stroke.
abstract: Receptor-associated protein (RAP) is a receptor antagonist that inhibits ligand interactions with the receptors that belong to the low density lipoprotein receptor gene family. The low-density lipoprotein receptor-related protein 1 (LRP1) has a crucial role in regulating tissue plasminogen activator (t-PA) and plasminogen activator inhibitor (PAI-1) expression. Furthermore, the functional balance of these two proteins is directly associated with the initiation and development of cerebral ischemic stroke. In the present study, the effect of RAP post-treatment was investigated in a rat autologous thromboembolic model. The expression and activity of t-PA and PAI-1 were detected and the neurological function was tested. The results suggest that post-treatment with RAP is able to improve neurorecovery after ischemic stroke by decreasing vascular damage and regulating t-PA and PAI-1 expressions. Post-treatment with RAP promotes t-PA expression, suppresses PAI-1 expression, significantly improves functional outcomes and decreases the amount of TUNEL-positive cells. RAP-treated rats show lower intracranial hemoglobin levels and a smaller ischemic zone. In conclusion, post-treatment with RAP regulates t-PA and PAI-1 expressions and thereby contributes to the improvement of functional outcomes after cerebral ischemia. Our findings strongly suggest that RAP may be of value in neurorecovery after stroke.
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Dan-Dong
authors.initials: DD
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Hong-Gang
authors.initials: HG
authors.lastname: Pang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China. Electronic address: jinningsong@126.com.
authors.forename: Jin-Ning
authors.initials: JN
authors.lastname: Song
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Yong-Lin
authors.initials: YL
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Bin-Fei
authors.initials: BF
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Xu-Dong
authors.initials: XD
authors.lastname: Ma
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, Shaanxi, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Sun
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism*; D005786:Gene Expression Regulation; D026563:LDL-Receptor Related Protein-Associated Protein / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism*; D010959:Tissue Plasminogen Activator / Q000096:biosynthesis*
chemical_list: D026563:LDL-Receptor Related Protein-Associated Protein; D017395:Plasminogen Activator Inhibitor 1; D010959:Tissue Plasminogen Activator
keywords: Acute ischemic stroke; Hemorrhagic transformation; Neurorecovery; PAI-1; RAP; t-PA