title: 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.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jianjun
authors.initials: J
authors.lastname: Zhong
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Chongjie
authors.initials: C
authors.lastname: Cheng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Han
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Zhipeng
authors.initials: Z
authors.lastname: Teng
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Junchi
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Hongrong
authors.initials: H
authors.lastname: Zhang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Jinchuan
authors.initials: J
authors.lastname: Wu
authors.affiliation: Department of Cerebrovascular, The First Affiliated Hospital of Zunyi Medical College, Zunyi, Guizhou 653000, China.
authors.forename: Fang
authors.initials: F
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Li
authors.initials: L
authors.lastname: Jiang
authors.affiliation: Department of Neurosurgery, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, China.
authors.forename: Xiaochuan
authors.initials: X
authors.lastname: Sun
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D000077610:Bexarotene; D001921:Brain / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D000070642:Brain Injuries, Traumatic / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology / Q000523:psychology; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000473:pathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011897:Random Allocation; D065852:Spatial Memory / Q000187:drug effects / Q000502:physiology; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
chemical_list: D001057:Apolipoproteins E; D018696:Neuroprotective Agents; D013764:Tetrahydronaphthalenes; D000077610:Bexarotene; C505409:Casp3 protein, mouse; D053148:Caspase 3
keywords: apolipoprotein E; apoptosis; bexarotene; inflammation; traumatic brain injury