Insulin increases central apolipoprotein E levels as revealed by an improved technique for collection of cerebrospinal fluid from rats.

Insulin increases central apolipoprotein E levels as revealed by an improved technique for collection of cerebrospinal fluid from rats.
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DOI:
10.1016/j.jneumeth.2012.05.034
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发表时间:
2012-07-30
影响因子:
3
通讯作者:
Woods SC
Woods SC
中科院分区:
医学4区
文献类型:
--
作者:
Liu M;Shen L;Begg DP;D'alessio DA;Woods SC

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脑脊液(CSF)为中枢神经系统(CNS)提供了一个宝贵的分析窗口,因为它反映了CNS成分的动态变化。我们描述了一种改进的方法,采样CSF大鼠,很容易执行。它具有96%的CSF收集成功率,并持续产生大量(150-200 μl)CSF。血液污染率也很低(6%),这是通过目视检查和缺乏载脂蛋白B(一种血浆衍生蛋白,在CNS中不存在)的分子检测确定的。这种改进的CSF采样方法在不同CNS靶点的生理学和药理学评价中具有广泛的适用性。我们使用该技术通过检查腹腔注射胰岛素对CSF中载脂蛋白E(apoE)水平的影响来提供原理证明。胰岛素(0.5和1 U/kg)导致腹腔内给药后2 h血浆和CSF中胰岛素显著增加,血糖降低至少2 h。CSF中的ApoE浓度也显著升高,但血浆中的ApoE浓度未显著升高,其时间进程与2 h内血糖的变化呈负相关。这些结果为新型CSF采样和大鼠CSF采样验证程序提供了药理学验证。
Cerebrospinal fluid (CSF) provides an invaluable analytical window to the central nervous system (CNS) because it reflects the dynamically changing complement of CNS constituents. We describe an improved method for sampling CSF in rats that is easy to perform. It has a 96% success rate of CSF collection and consistently yields large volumes (150–200 μl) of CSF. The blood contamination rate is also low (6%) as determined by both visual inspection and the lack of molecular detection of apolipoprotein B, a plasma-derived protein, which is absent in the CNS. This improved method of CSF sampling can have broad applicability in physiological and pharmacological evaluation for diverse CNS targets. We used this technique to provide proof of principle by examining the effect of intraperitoneal insulin on the level of apolipoprotein E (apoE) in the CSF. Insulin (0.5 and 1 U/kg) led to a significant increase of insulin in both plasma and CSF at 2 h after intraperitoneal administration and decreased blood glucose for at least 2 h. ApoE concentrations in CSF, but not in plasma, were also significantly increased, and its time-course was inversely correlated with the alterations in blood glucose over 2 h. These results provide a pharmacological validation of the novel CSF sampling and validation procedure for sampling rat CSF.
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