Department of Anaesthesiology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ, Groningen, The Netherlands.
Department of Psychiatry, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Fluids Barriers CNS. 2023 Feb 13;20(1):13. doi: 10.1186/s12987-023-00413-8.
Potential biomarkers for neuropsychiatric disorders are cerebrospinal fluid (CSF) monoamines and their corresponding precursors and metabolites. During CSF sampling, CSF flows towards the lumbar sampling site from more cranial regions. To compare the results of studies in which different CSF volumes were acquired, it is important to know if ventricular-lumbar concentration gradients exist. This has only been addressed for a few biogenic amines, and almost exclusively in neurologically unwell patients due to the burden of a lumbar puncture (necessary to obtain CSF). The aim of our study was to determine if concentration gradients exist for routinely measured CSF constituents and biogenic amines in neurologically healthy patients. We applied a novel ultrasensitive liquid chromatography mass spectrometry (LC-MS/MS) method for the simultaneous quantification of multiple monoamines, precursors and metabolites in CSF and plasma.
CSF and blood samples were collected from twenty neurologically healthy patients undergoing spinal anaesthesia. Ten mL of lumbar CSF was collected in five consecutive two mL fractions. We determined leucocyte and erythrocyte counts, glucose, albumin and protein concentrations and quantified monoamines, precursors and metabolites on each of the fractions using LC-MS/MS.
In twenty patients (60% male; median age: 46 years), dopamine, DOPAC, 3-MT, HVA, noradrenaline, normetanephrine and 5-HIAA concentrations increased from the first to the last CSF fraction (all p < 0.001). CSF adrenaline concentrations were below the detection limit, whereas serotonin measurements were regarded as unreliable. Albumin and total protein levels decreased significantly across CSF fractions.
A ventricular-lumbar CSF concentration gradient existed for most of the investigated analytes. This is a novel finding for dopamine, noradrenaline, 3-MT and normetanephrine. These results contribute to the understanding of the neurobiology and underline the importance of standardized procedures for CSF handling to allow comparisons between studies.
神经精神疾病的潜在生物标志物是脑脊液（CSF）单胺及其相应的前体和代谢物。在 CSF 采样过程中，CSF 从颅腔更高级别的区域流向腰椎采样部位。为了比较获取不同 CSF 量的研究结果，如果存在脑室-腰椎浓度梯度，则很重要。这仅针对少数几种生物胺进行了研究，而且由于腰椎穿刺（获得 CSF 所需）的负担，几乎仅在神经功能障碍的患者中进行。我们研究的目的是确定在神经健康患者中，常规测量的 CSF 成分和生物胺是否存在浓度梯度。我们应用了一种新的超灵敏液相色谱-质谱（LC-MS/MS）方法，同时定量 CSF 和血浆中的多种单胺、前体和代谢物。
从 20 名接受脊髓麻醉的神经健康患者中采集 CSF 和血液样本。在连续的五个 2ml 部分中收集 10ml 的腰椎 CSF。我们确定了白细胞和红细胞计数、葡萄糖、白蛋白和蛋白质浓度，并使用 LC-MS/MS 对每个部分的单胺、前体和代谢物进行了定量。
在 20 名患者（60%为男性；中位年龄：46 岁）中，多巴胺、DOPAC、3-MT、HVA、去甲肾上腺素、去甲肾上腺素和 5-HIAA 浓度从第一份 CSF 样本到最后一份 CSF 样本均增加（均 p<0.001）。CSF 肾上腺素浓度低于检测限，而 5-HT 测量被认为不可靠。CSF 白蛋白和总蛋白水平随 CSF 样本分数的减少而显著降低。
大多数研究分析物存在脑室-腰椎 CSF 浓度梯度。这是多巴胺、去甲肾上腺素、3-MT 和去甲肾上腺素的新发现。这些结果有助于理解神经生物学，并强调了标准化 CSF 处理程序的重要性，以允许在研究之间进行比较。
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