Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α

BMC Neuroscience

Ching-Ping Chang¹  Chung-Zhing Yang³  Bor-Chih Cheng³  Chien-Ming Chao²  Chong-Un Cheong⁴  Che-Chuan Wang⁵  Chin-Hong Chang⁵  Chung-Ching Chio⁵ 

[1] Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan;Department of Surgery and Department of Intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;The PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan;Department of Intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan;Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan

关键词: Neuron;    Astrocyte;    Tumor necrosis factor-alpha;    Microglia;    Traumatic brain injury;   

Others  :  1140383
DOI  :  10.1186/1471-2202-14-33

 received in 2012-11-08, accepted in 2013-03-07,  发布年份 2013

【 摘 要 】

Background

Tumor necrosis factor-alpha (TNF-α) is elevated early in injured brain after traumatic brain injury (TBI), in humans and in animals. Etanercept (a TNF-α antagonist with anti-inflammatory effects) attenuates TBI in rats by reducing both microglial and astrocytic activation and increased serum levels of TNF-α. However, it is not known whether etanercept improves outcomes of TBI by attenuating microglia-associated, astrocytes-associated, and/or neurons-associated TNF-α expression in ischemic brain. A well clinically relevant rat model, where a lateral fluid percussion is combined with systemic administration of etanercept immediately after TBI, was used. The neurological severity score and motor function was measured on all rats preinjury and on day 3 after etanercept administration. At the same time, the neuronal and glial production of TNF-α was measured by Immunofluorescence staining. In addition, TNFα contents of ischemic cerebral homogenates was measured using commercial enzyme-linked immunosorbent assay kits.

Results

In addition to inducing brain ischemia as well as neurological and motor deficits, TBI caused significantly higher numbers of microglia-TNF-α double positive cells, but not neurons-TNF-α or astrocytes-TNF-α double positive cells in the injured brain areas than did the sham operated controls, when evaluated 3 days after TBI. The TBI-induced cerebral ischemia, neurological motor deficits, and increased numbers of microglia-TNF-α double positive cells and increased TNF-α levels in the injured brain were all significantly attenuated by etanercept therapy.

Conclusion

This finding indicates that early microglia overproduction of TNF-α in the injured brain region after TBI contributes to cerebral ischemia and neurological motor deficits, which can be attenuated by etanercept therapy. Studies in this model could provide insight into the mechanisms underlying neurological motor disturbance in brain-injured patients.

【 授权许可】

   
2013 Chio et al.; licensee BioMed Central Ltd.

【 图 表 】

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