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Open Access Highly Accessed Research article

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

Chung-Ching Chio1, Chin-Hong Chang1, Che-Chuan Wang1, Chong-Un Cheong2, Chien-Ming Chao3, Bor-Chih Cheng15, Chung-Zhing Yang5 and Ching-Ping Chang4*

Author affiliations

1 Department of Surgery, Chi Mei Medical Center, Tainan, Taiwan

2 Department of Intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan

3 Department of Surgery and Department of Intensive Care Medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan

4 Department of Biotechnology, Southern Taiwan University of Science and Technology, Tainan, Taiwan

5 The PhD Program for Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan

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Citation and License

BMC Neuroscience 2013, 14:33  doi:10.1186/1471-2202-14-33

Published: 15 March 2013

Abstract

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.

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