title: Intravenous PEP-1-GDNF is protective after focal cerebral ischemia in rats.
abstract: Glial cell line-derived neurotrophic factor (GDNF) is a potential therapeutic protein on a variety of central nervous system diseases including ischemic stroke. However, GDNF is a large molecule that cannot cross the blood-brain barrier (BBB), which is still intact in the early hours after stroke when neural rescue is possible. PEP-1 protein transduction domain can deliver protein cargo across the cell membrane and the BBB. In the present study, we generated a novel fusion protein PEP-1-GDNF and examined whether PEP-1-GDNF is protective in focal cerebral ischemia. PEP-1-GDNF (200 μg/kg) or PBS was intravenously applied over 5 min immediately after reperfusion of 90 min transient middle cerebral artery occlusion (MCAO). After 28 days, rats were deeply anesthetized and decapitated. Behavioral tests were performed during this period. The results showed that PEP-1-GDNF significantly reduced the infarct volume and improved behavioral function. Further, PEP-1-GDNF promoted the cell proliferation and differentiation in the dentate gyrus of the hippocampus and attenuated ischemia-induced learning and memory damage.
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China.
authors.forename: Yaning
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Kai Nuo Bio. Sci. Co., Ltd., Guangzhou 510633, China.
authors.forename: Shangwu
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China.
authors.forename: Shijian
authors.initials: S
authors.lastname: Luo
authors.affiliation: Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-Sen University, Zhuhai 519000, China. Electronic address: lizdsysu@163.com.
authors.forename: Zhendong
authors.initials: Z
authors.lastname: Li
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Fengyin
authors.initials: F
authors.lastname: Liang
authors.affiliation: Kai Nuo Bio. Sci. Co., Ltd., Guangzhou 510633, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China. Electronic address: peizhong@mail.sysu.edu.cn.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Pei
authors.affiliation: Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Ruxun
authors.initials: R
authors.lastname: Huang
mesh_terms: D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000473:pathology; D020520:Brain Infarction / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation / Q000187:drug effects; D003543:Cysteamine / Q000031:analogs & derivatives*; D018891:Dentate Gyrus / Q000187:drug effects / Q000473:pathology; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics*; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007275:Injections, Intravenous; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010455:Peptides / Q000235:genetics*; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000627:therapeutic use*
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D018696:Neuroprotective Agents; C503924:Pep-1 peptide; D010455:Peptides; D011993:Recombinant Fusion Proteins; D003543:Cysteamine
keywords: Infarct volume; Neurogenesis; PEP-1-GDNF; Protein transduction domain; Stroke