Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis
Abnormalities in the cerebrospinal fluid levels of endocannabinoids in multiple sclerosis
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DOI：
10.1136/jnnp.2007.139071
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发表时间：
2008-11-01
影响因子：
11
通讯作者：
Sarchielli, P.
中科院分区：
文献类型：
--
作者：
Di Filippo, M.;Pini, L. A.;Sarchielli, P.
目的：内源性大麻素（eCB）在调节神经炎症中发挥作用，实验结果表明，它们可能直接参与多发性硬化症（MS）的发病机制。我们的研究的目的是测量eCB水平的MS患者的脑脊液（CSF）中。患者和方法：花生四烯酸乙醇胺（anandamide，AEA），palmotyethanolamide（PEA），2-花生四烯酸甘油（2-AG）和油酰乙醇胺（OEA）水平进行了测量，在50例MS患者和20例对照组的CSF同位素稀释气相色谱/质谱法。患者包括35例MS患者的复发缓解（RR）形式的疾病，20个在稳定的临床阶段和15在复发期间，和15例MS患者的继发性进展（SP）form.Results：所有测试的eCB的水平显着降低，发现在CSF中的MS患者相比，对照组，SP MS组检测到较低的值。较高水平的AEA和PEA，虽然低于对照组，被发现在复发期间的RR MS患者的CSF。较高水平的AEA，2-AG和OEA被发现在MRI钆增强（Gd+）lesions.Discussion的患者：目前的研究结果表明，存在一个受损的eCB系统在MS。增加CSF水平的AEA复发期间或在RR患者Gd+病变表明其潜在的作用，在限制正在进行的炎症过程与潜在的神经保护的影响。这些发现为靶向eCB的药物的开发提供了进一步的支持，作为一种潜在的药理学策略，以减轻MS的症状和减缓疾病进展。
Objective: Endocannabinoids (eCBs) play a role in the modulation of neuroinflammation, and experimental findings suggest that they may be directly involved in the pathogenesis of multiple sclerosis ( MS). The objective of our study was to measure eCB levels in the cerebrospinal fluid (CSF) of patients with MS.Patients and methods: Arachidonoylethanolamine ( anandamide, AEA), palmotylethanolamide (PEA), 2-arachidonoylglycerol (2-AG) and oleoylethanolamide (OEA) levels were measured in the CSF of 50 patients with MS and 20 control subjects by isotope dilution gaschromatography/mass-spectrometry. Patients included 35 patients with MS in the relapsing-remitting (RR) form of the disease, 20 in a stable clinical phase and 15 during a relapse, and 15 patients with MS in the secondary progressive (SP) form.Results: Significantly reduced levels of all the tested eCBs were found in the CSF of patients with MS compared to control subjects, with lower values detected in the SP MS group. Higher levels of AEA and PEA, although below those of controls, were found in the CSF of RR MS patients during a relapse. Higher levels of AEA, 2-AG and OEA were found in patients with MRI gadolinium-enhancing (Gd+) lesions.Discussion: The present findings suggest the presence of an impaired eCB system in MS. Increased CSF levels of AEA during relapses or in RR patients with Gd+ lesions suggest its potential role in limiting the ongoing inflammatory process with potential neuroprotective implications. These findings provide further support for the development of drugs targeting eCBs as a potential pharmacological strategy to reduce the symptoms and slow disease progression in MS.