Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury
Remodeling of cerebrospinal fluid lipoprotein particles after human traumatic brain injury
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DOI：
10.1089/089771503767869953
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发表时间：
2003-08-01
影响因子：
4.2
通讯作者：
Caslake, MJ
中科院分区：
文献类型：
--
作者：
Kay, AD;Day, SP;Caslake, MJ
具有APOE ε 4等位基因与创伤性脑损伤（TBI）后不利结果之间的关联表明载脂蛋白E蛋白（apoE）在人脑对损伤的反应中起关键作用。已知ApoE通过其作为受体介导的脂蛋白颗粒（LPS）摄取的配体的作用来调节外周中的胆固醇代谢。更好地了解人类中枢神经系统中的胆固醇代谢可能会发现适用于急性脑损伤的新治疗策略。我们报告的结果，从分析的脑脊液（CSF）中的TBI和非受伤的控制患者，测试的假设，CSF脂蛋白的重塑反映了脑TBI的反应。通过尺寸排阻色谱法从对照组和重度TBI患者的CSF中分离CSF LPS，并分析脂蛋白组分的胆固醇、磷脂、apoAI和apoE。与对照组相比，TBI CSF中含apoE的LPS显著降低（P = 0.002）。TBI后，含载脂蛋白I的CSF Lps（CSF LpAI）没有显著降低，但载脂蛋白AI存在于比对照CSF更小的颗粒上。在TBI CSF中存在非常小尺寸的Lp群体，其与TBI后观察到的胆固醇（P = 0.0001）和磷脂（p = 0.040）增加相关。从CSF中含有apoE的LPS的急剧损失和CSF胆固醇的显著增加支持了apoE和胆固醇代谢在急性脑损伤的背景下密切相关的概念。针对神经元发芽和突触发生所需的CNS脂质转运的治疗策略可能适用于创伤性脑损伤。
The association between possession of the APOE epsilon4 allele and unfavourable outcome after traumatic brain injury (TBI) suggests that the apolipoprotein E protein (apoE) plays a key role in the response of the human brain to injury. ApoE is known to regulate cholesterol metabolism in the periphery through its action as a ligand for receptor mediated uptake of lipoprotein particles (Lps). Greater understanding of cholesterol metabolism in the human central nervous system may identify novel treatment strategies applicable to acute brain injury. We report findings from the analysis of lipoproteins in the cerebrospinal fluid (CSF) of patients with TBI and non-injured controls, testing the hypothesis that remodeling of CSF lipoproteins reflects the response of the brain to TBI. CSF Lps were isolated from the CSF of controls and patients with severe TBI by size exclusion chromatography, and the lipoprotein fractions analysed for cholesterol, phospholipid, apoAI, and apoE. There was a marked decrease in apoE containing Lps in the TBI CSF compared to controls (P = 0.002). After TBI there was no significant decrease in apoI containing CSF Lps (CSF LpAI), but the apoAI resided on smaller sized particles than in control CSF. There was a population of very small sized Lps in TBI CSF, which were associated with the increased cholesterol (P = 0.0001) and phospholipid (p = 0.040) seen after TBI. The dramatic loss of apoE containing Lps from the CSF, and the substantial increase in CSF cholesterol, support the concept that apoE and cholesterol metabolism are intimately linked in the context of acute brain injury. Treatment strategies targeting CNS lipid transport, required for neuronal sprouting and synaptogenesis, may be applicable to traumatic brain injury.