ApoE Influences the Blood-Brain Barrier Through the NF-κB/MMP-9 Pathway After Traumatic Brain Injury
Autor: | Chongjie Cheng, Chao Luo, Xiaochuan Sun, Shuang Tang, Li Jiang, Zhijian Huang, Jianjun Zhong, Xing Peng, Zongduo Guo, Yue Wu, Zhipeng Teng, Haitao Wu |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Genetically modified mouse Apolipoprotein E medicine.medical_specialty Traumatic brain injury Science Transgene Brain Edema Mice Transgenic Blood–brain barrier Article Mice 03 medical and health sciences Apolipoproteins E 0302 clinical medicine In vivo Internal medicine Brain Injuries Traumatic medicine Animals Multidisciplinary Tight junction business.industry NF-kappa B Wild type medicine.disease Surgery Disease Models Animal 030104 developmental biology medicine.anatomical_structure Endocrinology Matrix Metalloproteinase 9 nervous system Blood-Brain Barrier Medicine business 030217 neurology & neurosurgery Signal Transduction |
Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-8 (2017) Scientific Reports |
ISSN: | 2045-2322 |
Popis: | Apolipoprotein E (ApoE), encoded by the ApoE gene (APOE), influences the outcomes of traumatic brain injury (TBI), but the mechanism remains unclear. The present study aimed to investigate the effects of different ApoEs on the outcome of TBI and to explore the possible mechanisms. Controlled cortical impact (CCI) was performed on APOEε3 (E3) and APOEε4 (E4) transgenic mice, APOE-KO (KO) mice, and wild type (WT) mice to construct an in vivo TBI model. Neurological deficits, blood brain barrier (BBB) permeability and brain edema were detected at days 1, 3, and 7 after TBI. The results revealed no significant differences among the four groups at day 1 or day 3 after injury, but more severe deficits were found in E4 and KO mice than in E3 and WT mice. Furthermore, a significant loss of tight junction proteins was observed in E4 and KO mice compared with E3 and WT mice at day 7. Additionally, more expression and activation of NF-κB and MMP-9 were found in E4 mice compared with E3 mice. Different ApoEs had distinct effects on neuro-function and BBB integrity after TBI. ApoE3, but not E4, might inhibit the NF-κB/MMP-9 pathway to alleviate BBB disruption and improve TBI outcomes. |
Databáze: | OpenAIRE |
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