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Title: Induction of angiogenesis and modulation of vascular endothelial growth factor receptor-2 by simvastatin after traumatic brain injury. Author: Wu H, Jiang H, Lu D, Qu C, Xiong Y, Zhou D, Chopp M, Mahmood A. Journal: Neurosurgery; 2011 May; 68(5):1363-71; discussion 1371. PubMed ID: 21307798. Abstract: BACKGROUND: Our previous studies demonstrated that simvastatin reduced neuronal death, increased neurogenesis, and promoted functional recovery after traumatic brain injury (TBI). OBJECTIVE: To investigate the effect of simvastatin on angiogenesis after TBI and the related signaling pathways. METHODS: Saline or simvastatin (1 mg/kg) was administered orally to rats starting at day 1 after TBI or sham surgery and then daily for 14 days. Rats were sacrificed at 3 and 14 days after treatment. Brain sections and tissues were prepared for immunohistochemical staining, enzyme-linked immunosorbent assay, and Western blot analysis. Cultured rat brain microvascular endothelial cells were subjected to oxygen-glucose deprivation followed by immunocytochemical staining with phallotoxins and vascular endothelial growth factor receptor-2 (VEGFR-2). Western blot analysis was carried out to examine the simvastatin-induced activation of the v-akt murine thymoma viral oncogene homolog (Akt) signaling pathway. The expression of VEGFR-2 was detected by enzyme-linked immunosorbent assay. RESULTS: Simvastatin significantly increased the length of vascular perimeter, promoted the proliferation of endothelial cells, and improved the sensorimotor function after TBI. Simvastatin stimulated endothelial cell tube formation after oxygen-glucose deprivation in vitro. VEGFR-2 expression in both brain tissues and cultured rat brain microvascular endothelial cells was enhanced after simvastatin treatment, which may be modulated by activation of Akt. Akt-dependent endothelial nitric oxide synthase phosphorylation was also induced by simvastatin in vivo and in vitro. CONCLUSION: Simvastatin augments TBI-induced angiogenesis in the lesion boundary zone and hippocampus and improves functional recovery. Simvastatin also promotes angiogenesis in vitro. These beneficial effects on angiogenesis may be related to simvastatin-induced activation of the VEGFR-2/Akt/endothelial nitric oxide synthase signaling pathway.[Abstract] [Full Text] [Related] [New Search]