Kay A D, Day S P, Nicoll J A R, Packard C J, Caslake M J
Department of Neurosurgery, University of Glasgow, Institute of Neurological Sciences, Southern General Hospital, Glasgow G51 4TF, UK.
Atherosclerosis. 2003 Sep;170(1):141-6. doi: 10.1016/s0021-9150(03)00249-1.
Lipoprotein particles (Lps) in normal human cerebrospinal fluid (CSF) are distinct from those found in plasma and include unique apolipoprotein E (apoE indicates protein; APOE, gene) containing lipoproteins rarely seen in human plasma. Less favourable neurological recovery after subarachnoid hemorrhage (SAH) has been observed in patients who possess the APOE epsilon4 allele raising the possibility that apoE influences neuronal survival after brain injury. We analysed Lps from control and SAH CSF testing the hypotheses that following brain injury CSF Lps undergo remodelling and apoE containing Lps are selectively depleted from brain injury CSF. Lipoproteins were fractionated using CSF from six control pools and six patients with SAH on a sepharose 6HR 10/30 size exclusion column. Fractions were assayed for total cholesterol (TC), free cholesterol (FC), phospholipid, triglyceride (TG), apoE, apolipoprotein B (apoB), and apolipoprotein AI (apoAI). Compared to control CSF there were significant (P<0.05) increases in TC, FC, TG, and apoAI in SAH CSF. Plasma sized apoB-containing lipoproteins and a very small apoAI-containing Lps were identified in the SAH CSF, which were not present in controls. However, despite the release of plasma lipoproteins into the subarachnoid space, there was no significant increase in CSF apoE. These data provide novel indirect evidence suggesting that after SAH CSF Lps undergo remodelling and apoE containing Lps are selectively reduced in brain injury CSF. The remodelling of CSF Lps and selective reduction of apoE containing lipoproteins may reflect an important response of the human brain to injury.
正常人类脑脊液（CSF）中的脂蛋白颗粒（Lps）与血浆中的不同，包括独特的载脂蛋白E（apoE表示蛋白质；APOE表示基因），其含有的脂蛋白在人类血浆中很少见。在患有APOE ε4等位基因的蛛网膜下腔出血（SAH）患者中观察到较差的神经功能恢复，这增加了apoE影响脑损伤后神经元存活的可能性。我们分析了对照和SAH脑脊液中的Lps，检验了以下假设：脑损伤后CSF Lps会发生重塑，且含apoE 的Lps会从脑损伤脑脊液中选择性减少。使用来自六个对照样本池和六名SAH患者的脑脊液在琼脂糖6HR 10/30尺寸排阻柱上对脂蛋白进行分级分离。对各组分检测总胆固醇（TC）、游离胆固醇（FC）、磷脂、甘油三酯（TG）、apoE、载脂蛋白B（apoB）和载脂蛋白AI（apoAI）。与对照脑脊液相比，SAH脑脊液中的TC、FC、TG和apoAI显著增加（P<0.05）。在SAH脑脊液中鉴定出了血浆大小的含apoB脂蛋白和非常小的含apoAI的Lps，而对照中不存在这些。然而，尽管血浆脂蛋白释放到蛛网膜下腔，但脑脊液apoE没有显著增加。这些数据提供了新的间接证据，表明SAH后脑脊液Lps会发生重塑，且含apoE的Lps在脑损伤脑脊液中会选择性减少。脑脊液Lps的重塑和含apoE脂蛋白的选择性减少可能反映了人类大脑对损伤的重要反应。
