Dong Wang1, Tuo Li2, Huijie Wei3, Yi Wang4, Guili Yang5, Ye Tian6, Zilong Zhao7, Liang Wang8, Shengping Yu9, Yongqiang Zhang10, Jieli Chen11, Rongcai Jiang12, Jian Ning Zhang13. 1. 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. 2. 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. 3. 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. 4. 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. 5. Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: yangguili1985@163.com. 6. 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. 7. 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. 8. Department of Neurosurgery, Tianjin 5th Center Hospital, Tianjin, China. Electronic address: 757171007@qq.com. 9. Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: yshpvip@sina.com. 10. Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: friskyzyq@163.com. 11. Department of Neurology, Henry Ford Hospital, Detroit, USA. Electronic address: jieli@neuro.hfh.edu. 12. Department of Neurosurgery, Tianjin Key Laboratory of Injuries, Variations and Regeneration of Nervous System, Tianjin Neurological Institute, Tianjin, China. Electronic address: jiang116216@163.com. 13. 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.
Abstract
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.
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.