Etanercept attenuates traumatic brain injury in rats by reducing early microglial expression of tumor necrosis factor-α
| Autor: | Chien-Ming Chao, Chung-Ching Chio, Che-Chuan Wang, Chin-Hong Chang, Chong-Un Cheong, Chung-Zhing Yang, Ching-Ping Chang, Bor-Chih Cheng |
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| Rok vydání: | 2013 |
| Předmět: |
Male
Pathology medicine.medical_specialty Time Factors Traumatic brain injury Ischemia Tetrazolium Salts Nerve Tissue Proteins Receptors Tumor Necrosis Factor Etanercept Rats Sprague-Dawley Brain ischemia Cellular and Molecular Neuroscience medicine Animals Microglia Tumor Necrosis Factor-alpha business.industry General Neuroscience Anti-Inflammatory Agents Non-Steroidal Calcium-Binding Proteins Microfilament Proteins Neuron medicine.disease Rats Disease Models Animal medicine.anatomical_structure nervous system Gene Expression Regulation Brain Injuries Immunoglobulin G Tumor necrosis factor alpha Nervous System Diseases Astrocyte business Research Article medicine.drug |
| Zdroj: | BMC Neuroscience |
| ISSN: | 1471-2202 |
| DOI: | 10.1186/1471-2202-14-33 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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