STUDY DESIGN: Animal model of compressive spinal cord injury (SCI), reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization (ISH), immunohistochemistry (IHC) and enzymehistochemistry (EHC) were used to test the hypothesis that hypoxia-inducible factor-1alpha (HIF-1alpha) and the target genes activated by HIF-1alpha are involved in cell hypoxia tolerance and tissue vascularity to help injured tissue to go through the stress disease. OBJECTIVE: To determine whether HIF-1alpha and its target genes associated with hypoxia tolerance and neovascularization take part in the pathophysiological procedure of SCI in rats. SETTING: Yunnan University, China. METHODS: Random-bred adult male Sprague-Dawley (SD) rats weighing 250+/-50 g were prepared for compressive SCI models. After receiving compressive injury at T(10), rats were sacrificed at different times from 6 h to 1 week after injury. The injured cords were removed, and HIF-1alpha and its target genes were assayed by RT-PCR, ISH, IHC and EHC. The data were statistically analyzed. RESULTS: An increase in HIF-1alpha mRNA expression was observed 12 h postinjury, reached a maximum at 3 days, and reduced gradually thereafter. HIF-1alpha protein expressed earlier than HIF-1alpha mRNA. Additionally, two glycolytic enzymes and vascular endothelial growth factor (VEGF), which are regulated by HIF-1alpha, also increased after an interval postinjury, and their expression patterns shared a same trend with that of HIF-1alpha protein. CONCLUSION: The findings suggested that the most important hypoxic regulatory factor HIF-1alpha was upregulated in involved cells by activating the transcription and increasing protein stability, and subsequently activated the expression of HIF-1alpha target genes, including glycolytic enzymes and VEGF in SCI. Combined with the pathologic observation, it suggested that overexpression of HIF-1alpha and its target genes might take part in hypoxia tolerance and vascularity of the injured spinal cord.
STUDY DESIGN: Animal model of compressive spinal cord injury (SCI), reverse transcription-polymerase chain reaction (RT-PCR), in situ hybridization (ISH), immunohistochemistry (IHC) and enzymehistochemistry (EHC) were used to test the hypothesis that hypoxia-inducible factor-1alpha (HIF-1alpha) and the target genes activated by HIF-1alpha are involved in cell hypoxia tolerance and tissue vascularity to help injured tissue to go through the stress disease. OBJECTIVE: To determine whether HIF-1alpha and its target genes associated with hypoxia tolerance and neovascularization take part in the pathophysiological procedure of SCI in rats. SETTING: Yunnan University, China. METHODS: Random-bred adult male Sprague-Dawley (SD) rats weighing 250+/-50 g were prepared for compressive SCI models. After receiving compressive injury at T(10), rats were sacrificed at different times from 6 h to 1 week after injury. The injured cords were removed, and HIF-1alpha and its target genes were assayed by RT-PCR, ISH, IHC and EHC. The data were statistically analyzed. RESULTS: An increase in HIF-1alpha mRNA expression was observed 12 h postinjury, reached a maximum at 3 days, and reduced gradually thereafter. HIF-1alpha protein expressed earlier than HIF-1alpha mRNA. Additionally, two glycolytic enzymes and vascular endothelial growth factor (VEGF), which are regulated by HIF-1alpha, also increased after an interval postinjury, and their expression patterns shared a same trend with that of HIF-1alpha protein. CONCLUSION: The findings suggested that the most important hypoxic regulatory factor HIF-1alpha was upregulated in involved cells by activating the transcription and increasing protein stability, and subsequently activated the expression of HIF-1alpha target genes, including glycolytic enzymes and VEGF in SCI. Combined with the pathologic observation, it suggested that overexpression of HIF-1alpha and its target genes might take part in hypoxia tolerance and vascularity of the injured spinal cord.
Authors: Chirag B Patel; David M Cohen; Pallavi Ahobila-Vajjula; Laura M Sundberg; Tessy Chacko; Ponnada A Narayana Journal: J Neurotrauma Date: 2009-07 Impact factor: 5.269
Authors: O Nesic; J Lee; G C Unabia; K Johnson; Z Ye; L Vergara; C E Hulsebosch; J R Perez-Polo Journal: J Neurochem Date: 2008-01-28 Impact factor: 5.372
Authors: O Nesic; J D Guest; D Zivadinovic; P A Narayana; J J Herrera; R J Grill; V U L Mokkapati; B B Gelman; J Lee Journal: Neuroscience Date: 2010-01-28 Impact factor: 3.590
Authors: Femke Streijger; Ward T Plunet; Jae H T Lee; Jie Liu; Clarrie K Lam; Soeyun Park; Brett J Hilton; Bas L Fransen; Keely A J Matheson; Peggy Assinck; Brian K Kwon; Wolfram Tetzlaff Journal: PLoS One Date: 2013-11-04 Impact factor: 3.240