title: Administration of sonic hedgehog protein induces angiogenesis and has therapeutic effects after stroke in rats.
abstract: The Sonic hedgehog (Shh) signaling pathway is recapitulated in response to ischemic injury. Here, we investigated the clinical implications of Shh protein in the ischemic stroke and explored the underlying mechanism. Intracerebroventricular injection of Shh, Cyclopamine, or anti-vascular endothelial growth factor (VEGF) was performed immediately after permanent middle cerebral artery occlusion (pMCAO) surgery and lasted for 7days (d). Phosphate-buffered saline (PBS) was used as control. Neurological deficits and infarct volume were examined 7d after pMCAO. Microvascular density with fluorescein-iso-thiocyanate (FITC) assay and double staining with CD31 and Ki-67 was measured at 7d. To observe in vitro angiogenesis, rat brain microvascular endothelial cells (RBMECs) were incubated under oxygen glucose deprivation (OGD) for 6h (h) and treated with Shh/anti-VEGF. We found that (1) Shh improved neurological scores and reduced infarct volume, which was blocked by Cyclopamine, (2) Shh improved the microvascular density and promoted angiogenesis and neuron survival in the ischemic boundary zone, (3) Shh enhanced VEGF expression and VEGF antibody could reverse angiogenic and protective effect of Shh in vivo and in vitro. These data demonstrate that the administration of Shh protein could protect brain from ischemic injury, in part by promoting angiogenic repair.
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Sheng-Cai
authors.initials: SC
authors.lastname: Chen
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Neurology, The First Hospital of Yichang, Institute of Translational Neuroscience, Three Gorges University College of Medicine, Yichang 443002, China.
authors.forename: Ming
authors.initials: M
authors.lastname: Huang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Quan-Wei
authors.initials: QW
authors.lastname: He
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Elvis Nana
authors.initials: EN
authors.lastname: Opoku
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Hang
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.
authors.forename: Hui-Juan
authors.initials: HJ
authors.lastname: Jin
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: xiayuanpeng@mail.hust.edu.cn.
authors.forename: Yuan-Peng
authors.initials: YP
authors.lastname: Xia
authors.affiliation: Department of Neurology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. Electronic address: hubo@mail.hust.edu.cn.
authors.forename: Bo
authors.initials: B
authors.lastname: Hu
mesh_terms: D043925:Angiogenesis Inducing Agents / Q000627:therapeutic use*; D000818:Animals; D001921:Brain / Q000033:anatomy & histology; D020520:Brain Infarction / Q000209:etiology; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002766:Cholecystokinin / Q000378:metabolism; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D004398:Dyneins / Q000235:genetics / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects; D053823:Hedgehog Proteins / Q000378:metabolism / Q000627:therapeutic use*; D008297:Male; D009389:Neovascularization, Pathologic / Q000188:drug therapy* / Q000209:etiology*; D000072081:Patched-1 Receptor / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology; D020521:Stroke / Q000150:complications* / Q000188:drug therapy; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D043925:Angiogenesis Inducing Agents; D053823:Hedgehog Proteins; D000072081:Patched-1 Receptor; D010446:Peptide Fragments; D042461:Vascular Endothelial Growth Factor A; C410885:cholecystokinin 8; D002766:Cholecystokinin; D004398:Dyneins
keywords: VEGF antibody; angiogenesis; cerebral ischemia; sonic hedgehog