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Dual neuronal response to tumor necrosis factor-alpha following spinal cord injury

Neural Regeneration Research 2010年第12期5卷 917-926页

作者： Lingyi ChiO Jin YuO Hong ZhuO Xingang Li Shugan Zhu Zhenzhong Li L. Creed PetticlrewO david grasso James J. HickmanO Mark S. KindyO Department of Neurosurgery Qilu Hospital of Shandong University Jinan 250012 Shandong Province China Laboratory of Neurosurgery Qilu Hospital of Shandong University Jinan 250012 Shandong Province China Department of Neurosciences Medical University of South Carolina Charleston 29425 South Carolina USA Department of Anatomy Shandong University School of Medicine Jinan 250012 Shandong Province China Stroke Program Sanders-Brown Center on Aging University of Kentucky College of Medicine Lexington Kentucky Department of Veterans Affairs Medical Center Lexington 40536 Kentucky USA Xenogen Corporation 5 Cedar Brook Drive Cranbury 08512 New Jersey USA NanoScience Technology Center University of Florida Orlando 32826 Florida USA Ralph H. Johnson VA Medical Center Charleston 29401 South Carolina USA

BACKGROUND： Numerous studies have shown that tumor necrosis factor α （TNF-α） is closely correlated with spinal cord injury （SCI）, but the mechanisms of TNF-α and therapeutic treatments for SCI are still poorly understood. OBJECTIVE： To determine the role of TNF-α in the pathogenesis of SCI. DESIGN, TIME AND SETTING： An in vivo experiment based on genetically engineered animals was performed at the Medical University of South Carolina, Charleston, South Carolina, USA, between June 2007 and October 2008. MATERIALS： TNF-α transgenic rats （Xenogen Biosciences in Cranbury, New Jersey, USA） were utilized in this study. METHODS： TNF-α transgenic （tg） and wild-type （WT） rats underwent a complete single-level laminectomy at the 10^th thoracic vertebra （T10）. MAIN OUTCOME MEASURES： Motor function of rat hindlimb was assessed using the Basso, Beattie, and Bresnahan hindlimb locomotor rating scale. Histological evaluation of spinal cord tissue loss was conducted. Immunohistochemistry for astrocytes, microglia/macrophages, and TNF receptors （TNFRs） was performed on spinal cord tissue sections. TNF-α mRNA expression was detected by real-time polymerase chain reaction. The concentrations of nerve growth factor （NGF） and brain-derived neurotrophic factor （BDNF） in the supernatant were determined using an enzyme-linked immunosorbent assay kit for rat NGF or BDNF, respectively. The rats were injected subcutaneously with etanercept to verify that TNF-α was the direct effect of the modulation of behavioral and neurodegenerative outcomes in the TNF-α tg rats. RESULTS： TNF-α tg rats showed higher expression of TNF-α mRNA in the spinal cord prior to SCI. TNF-α tg rats showed worse motor deficits than WT rats in the acute period （〈 3 days） after SCI （P 〈 0.01）, while in the chronic period, TNF-α tg rats exhibited persistent elevated baseline levels of TNF-α mRNA and improved recovery in motor function and tissue healing compared to WT rats （P 〈 0.01 ）. Following SCI, the number of microgli

关键词： spinal cord injury tumor necrosis factor-α rats inflammation motor function astrocytes microglia nerve growth factor brain-derived neurotrophic factors

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