Atorvastatin enhances angiogenesis to reduce subdural hematoma in a rat model

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Journal of the neurological sciences


BACKGROUND AND PURPOSE: 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.

Medical Subject Headings

AC133 Antigen; Analysis of Variance; Angiopoietin-1; Animals; Anticholesteremic Agents; Antigens, CD34; Atorvastatin; Disease Models, Animal; Dose-Response Relationship, Drug; Endothelial Progenitor Cells; Gene Expression Regulation; Hematoma, Subdural; Magnetic Resonance Imaging; Male; Matrix Metalloproteinase 9; Microscopy, Electron, Transmission; Neovascularization, Physiologic; RNA, Messenger; Rats; Rats, Wistar; Time Factors; Vascular Endothelial Growth Factor A

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