Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.
Apolipoprotein E as a novel therapeutic neuroprotection target after traumatic spinal cord injury.
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DOI：
10.1016/j.expneurol.2017.10.014
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发表时间：
2018-01
影响因子：
5.3
通讯作者：
Cao Q
中科院分区：
文献类型：
--
作者：
Cheng X;Zheng Y;Bu P;Qi X;Fan C;Li F;Kim DH;Cao Q
载脂蛋白E（apoE）是一种血浆脂蛋白，在脂质和胆固醇代谢中起重要作用，也与许多神经系统疾病有关。在这项研究中，我们研究了载脂蛋白E对创伤性脊髓损伤（SCI）的病理生理学的影响。ApoE缺陷型突变体（apoE−/−）和野生型小鼠接受T9中度挫伤SCI，并在损伤后进行组织学和行为学分析。损伤后3天，apoE−/−小鼠的脊髓血屏障通透性（通过Evans蓝染料外渗测量）与野生型相比显著增加。与野生型小鼠相比，apoE−/−小鼠的炎症和备用白色物质也分别显著增加和减少。在apoE−/−小鼠中，神经元和少突胶质细胞的凋亡也显著增加。在损伤后42天，apoE−/−小鼠受损脊髓中的炎症仍然很强，但野生型小鼠则没有。来自外周血的CD 45+白细胞持续存在于apoE−/−小鼠受损的脊髓中。与野生型小鼠相比，apoE−/−小鼠的备用白色物质显著减少。从挫伤后第1周至第8周，apoE−/−小鼠的运动功能与野生型小鼠相比显著降低。外源性apoE模拟肽的治疗部分恢复了SCI后apoE−/−小鼠脊髓血屏障的通透性。重要的是，外源性apoE肽减少炎症，增加备用白色物质，促进SCI后apoE−/−小鼠的运动恢复。结果表明，内源性apoE在维持脊髓血屏障、减轻炎症反应和脊髓组织损伤中起重要作用，提示其在脊髓损伤后具有重要的神经保护作用。我们的结果进一步表明，外源性apoE模拟肽可能是一种新的和有前途的脊髓损伤的神经保护剂。
Apolipoprotein E (apoE), a plasma lipoprotein well known for its important role in lipid and cholesterol metabolism, has also been implicated in many neurological diseases. In this study, we examined the effect of apoE on the pathophysiology of traumatic spinal cord injury (SCI). ApoE-deficient mutant (apoE−/−) and wild-type mice received a T9 moderate contusion SCI and were evaluated using histological and behavioral analyses after injury. At 3 days after injury, the permeability of spinal cord-blood-barrier, measured by extravasation of Evans blue dye, was significantly increased in apoE−/− mice compared to wild type. The inflammation and spared white matter was also significantly increased and decreased, respectively, in apoE−/− mice compared to the wild type ones. The apoptosis of both neurons and oligodendrocytes was also significantly increased in apoE−/− mice. At 42 days after injury, the inflammation was still robust in the injured spinal cord in apoE−/− but not wild type mice. CD45+ leukocytes from peripheral blood persisted in the injured spinal cord of apoE−/− mice. The spared white matter was significantly decreased in apoE−/− mice compared to wild type ones. Locomotor function was significantly decreased in apoE−/− mice compared to wild type ones from week 1 to week 8 after contusion. Treatment of exogenous apoE mimetic peptides partially restored the permeability of spinal cord-blood-barrier in apoE−/− mice after SCI. Importantly, the exogenous apoE peptides decreased inflammation, increased spared white matter and promoted locomotor recovery in apoE−/− mice after SCI. Our results indicate that endogenous apoE plays important roles in maintaining the spinal cord-blood-barrier and decreasing inflammation and spinal cord tissue loss after SCI, suggesting its important neuroprotective function after SCI. Our results further suggest that exogenous apoE mimetic peptides could be a novel and promising neuroprotective reagent for SCI.
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影响因子：
12.7
作者：
Grinberg LT;Thal DR
通讯作者：
Thal DR
载脂蛋白 E-模拟 COG1410 可减轻创伤性脑损伤后的急性血管源性水肿
影响因子：
4.2
作者：
Cao, Fang;Jiang, Yong;Sun, Xiaochuan
通讯作者：
Sun, Xiaochuan
影响因子：
6.1
作者：
Fan C;Wang H;Chen D;Cheng X;Xiong K;Luo X;Cao Q
通讯作者：
Cao Q
影响因子：
4.2
作者：
Hoane MR;Kaufman N;Vitek MP;McKenna SE
通讯作者：
McKenna SE
影响因子：
5.3
作者：
Cao, QL;Zhang, YP;Whittemore, SR
通讯作者：
Whittemore, SR