Bexarotene protects against traumatic brain injury in mice partially through apolipoprotein E
| Autor: | Jianjun Zhong, Xiaochuan Sun, Junchi He, Li Jiang, Yue Wu, Chongjie Cheng, Hongrong Zhang, Han Liu, Zhijian Huang, Zhipeng Teng, Fang Cao, Jinchuan Wu |
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| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Apolipoprotein E Male Tetrahydronaphthalenes Traumatic brain injury Inflammation Apoptosis Pharmacology Motor Activity Neuroprotection Proinflammatory cytokine 03 medical and health sciences Random Allocation 0302 clinical medicine Apolipoproteins E Brain Injuries Traumatic medicine Animals Liver X receptor Spatial Memory Bexarotene Mice Knockout Microglia Chemistry Caspase 3 General Neuroscience Brain medicine.disease nervous system diseases Mice Inbred C57BL Disease Models Animal 030104 developmental biology medicine.anatomical_structure Neuroprotective Agents Immunology medicine.symptom 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Neuroscience. 343 |
| ISSN: | 1873-7544 |
| Popis: | Bexarotene has been proved to have neuroprotective effects in many animal models of neurological diseases. However, its neuroprotection in traumatic brain injury (TBI) is still unknown. This study aims to explore the neuroprotective effects of bexarotene on TBI and its possible mechanism. Controlled cortical impact (CCI) model was used to simulate TBI in C57BL/6 mice as well as APOE gene knockout (APOE-KO) mice. After CCI, mice were daily dosed with bexarotene or vehicle solution intraperitoneally. The motor function, learning and memory, inflammatory factors, microglia amount, apoptosis condition around injury site and main side-effects were all measured. The results showed that, after CCI, bexarotene treatment markedly improved the motor function and spatial memory in C57BL/6 compare to APOE-KO mice which showed no improvement. The inflammatory cytokines, microglia amount, cell apoptosis rate, and protein of cleaved caspase-3 around the injury site were markedly upregulated after TBI in both C57BL/6 and APOE-KO mice, and all these upregulation were significantly mitigated by bexarotene treatment in C57BL/6 mice, but not in APOE-KO mice. No side-effects were detected after consecutive administration. Taken together, bexarotene inhibits the inflammatory response as well as cell apoptosis and improves the neurological function of mice after TBI partially through apolipoprotein E. This may make it a promising candidate for the therapeutic treatment after TBI. |
| Databáze: | OpenAIRE |
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