Cerebral angiogenesis after collagenase-induced intracerebral hemorrhage in rats.
Spontaneous intracerebral hemorrhage (ICH) is one of the most devastating subtypes of stroke. Since angiogenesis is a fundamental process to brain development and repair by new blood vessel formation from pre-existing ones, mediated by numerous angiogenic factors including vascular endothelial growth factor (VEGF), the goal of the present work is to establish whether there is cerebral angiogenesis in rat brains with collagenase-induced ICH. Investigations were also performed to evaluate whether ICH alters expression of VEGF and its receptors Flt-1 and Flk-1. ICH was induced on adult male Sprague-Dawley rats by stereotactic injection of collagenase type VII into right globus pallidus. Angiogenesis was identified by hematoxylin-eosin stain and double immunolabeling method, and expression of VEGF and the receptors was evaluated by immunohistochemistry and quantitative real time reverse transcription-polymerase chain reaction. New vessels appeared around the hematoma and extended into it from 7 days, and 5-Bromo-2-Deoxyuridine-labeled nuclei in cerebral endothelial cells resided around the hematoma and the labeling peaked from 7 to 14 days. Expression of VEGF, Flt-1 and Flk-1 was observed in cerebral endothelial cells at the hemorrhagic basal ganglion, and increases of their mRNA persisted to 28 days. These findings suggest that ICH can induce cerebral angiogenesis and upregulation of VEGF, Flt-1 and Flk-1 and that modulation of angiogenesis via altering expression of VEGF and its receptors may be a potential strategy for promoting ICH repair.
Tang
Tao
T
Department of Neurology, Xiangya Hospital, Central South University, Changsha 410008, PR China. falcontang@126.com
Liu
Xiao-Juan
XJ
Zhang
Zong-Qi
ZQ
Zhou
Hua-Jun
HJ
Luo
Jie-Kun
JK
Huang
Ju-Fang
JF
Yang
Qi-Dong
QD
Li
Xing-Qun
XQ
D000818:Animals; D001921:Brain / Q000098:blood supply / Q000187:drug effects / Q000503:physiopathology; D002536:Cerebral Arteries / Q000166:cytology / Q000503:physiopathology; D002543:Cerebral Hemorrhage / Q000139:chemically induced / Q000473:pathology* / Q000503:physiopathology*; D017364:Collagenases; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D008297:Male; D008833:Microcirculation / Q000166:cytology / Q000503:physiopathology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000502:physiology*; D015854:Up-Regulation / Q000502:physiology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics / Q000378:metabolism
D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; C501164:Flt1 protein, rat; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2; D017364:Collagenases