Bexarotene protects against traumatic brain injury in mice partially through apolipoprotein E.

Abstract

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.

• Authors: Jianjun Zhong, Chongjie Cheng, Han Liu, Zhijian Huang, Yue Wu, Zhipeng Teng, Junchi He, Hongrong Zhang, Jinchuan Wu, Fang Cao, Li Jiang, Xiaochuan Sun
• Journal: Neuroscience (Neuroscience) Vol. 343 Pg. 434-448 (02 20 2017) ISSN: 1873-7544 [Electronic] United States
• PMID: 27235741 (Publication Type: Journal Article)
• Copyright: Copyright © 2016. Published by Elsevier Ltd.

Chemical References

• Apolipoproteins E
• Neuroprotective Agents
• Tetrahydronaphthalenes
• Bexarotene
• Casp3 protein, mouse
• Caspase 3

Topics

• Animals
• Apolipoproteins E (genetics, metabolism)
• Apoptosis (drug effects, physiology)
• Bexarotene
• Brain (drug effects, immunology, pathology)
• Brain Injuries, Traumatic (drug therapy, immunology, pathology, psychology)
• Caspase 3 (metabolism)
• Disease Models, Animal
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• Microglia (drug effects, immunology, pathology)
• Motor Activity (drug effects, physiology)
• Neuroprotective Agents (pharmacology)
• Random Allocation
• Spatial Memory (drug effects, physiology)
• Tetrahydronaphthalenes (pharmacology)