title: Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model.
abstract: OBJECTIVE
  Statins are active in reducing plasma lipids, suppressing inflammation and promoting angiogenesis. Because angiogenesis is critical for the absorbance of subdural hematoma (SDH), we hypothesize that atorvastatin promotes angiogenesis to enhance hematoma absorption.
  
  
  METHODS
  SDH was induced in adult Wistar rats and treated with 3mg/kg, 8mg/kg of atorvastatin, or vehicle saline daily for 7days. The treated rats were examined for the level of CD34+/CD133+ endothelial progenitor cells (EPCs) in the circulation by flow cytometry, hematoma volumes by magnetic resonance imaging (MRI), and changes in cognitive functions. We also examined angiogenesis in the hematoma wall by transmission electronic microscopy and immunohistochemistry for the expression of vascular endothelial growth factor (VEGF), matrix metalloprotease 9 (MMP 9) and angiopoietin.
  
  
  RESULTS
  SDH volume was significantly reduced and neurological deficits improved in rats receiving the low dose atorvastatin compared to those receiving either the high dose of atorvastatin or saline. Consistent with these outcome measures, the low dose atorvastatin increased the expression of angiopoient-1 and VEGF and reduced MMP9 expression in the connective tissue of the SDH wall, resulting in an increased vascular density and enhanced vascular maturation.
  
  
  CONCLUSIONS
  The low-dose atorvastatin is effective in reducing SDH and improving neurological deficits in a rat model, primarily by promoting angiogenesis and vascular maturation.
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: 54454241@qq.com.
authors.forename: Dong
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: lt19880619@sina.com.
authors.forename: Tuo
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: huijiewei@126.com.
authors.forename: Huijie
authors.initials: H
authors.lastname: Wei
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: sinuosiwo@sina.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: yangguili1985@163.com.
authors.forename: Guili
authors.initials: G
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: yetian1986@gmail.com.
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: ZilongZ@BloodWorksNW.org.
authors.forename: Zilong
authors.initials: Z
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Tianjin 5th Center Hospital, Tianjin, China. Electronic address: 757171007@qq.com.
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: yshpvip@sina.com.
authors.forename: Shengping
authors.initials: S
authors.lastname: Yu
authors.affiliation: Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: friskyzyq@163.com.
authors.forename: Yongqiang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Neurology, Henry Ford Hospital, Detroit, USA. Electronic address: jieli@neuro.hfh.edu.
authors.forename: Jieli
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: jiang116216@163.com.
authors.forename: Rongcai
authors.initials: R
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, Tianjin Medical University, General Hospital, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: jianningzhang@hotmail.com.
authors.forename: Jian Ning
authors.initials: JN
authors.lastname: Zhang
mesh_terms: D000071916:AC133 Antigen / Q000097:blood; D000704:Analysis of Variance; D042683:Angiopoietin-1 / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D018952:Antigens, CD34 / Q000097:blood; D000069059:Atorvastatin / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D066026:Endothelial Progenitor Cells / Q000187:drug effects / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000187:drug effects; D006408:Hematoma, Subdural / Q000000981:diagnostic imaging / Q000188:drug therapy*; D008279:Magnetic Resonance Imaging; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism
chemical_list: D000071916:AC133 Antigen; D042683:Angiopoietin-1; D000924:Anticholesteremic Agents; D018952:Antigens, CD34; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D000069059:Atorvastatin; D020780:Matrix Metalloproteinase 9
keywords: Angiogenesis; Atorvastatin; Rat model; Subdural hematoma